Brain Edema IX: Proceedings of the Ninth International Symposium Tokyo, May 16–19, 1993

584 Pages·1994·19.82 MB·English

by  Igor Klatzo M.D. (auth.)

BRAI EDEMA 1993
Brain Edema IX
Proceedings of the Ninth International Symposium
Mqy 16-19) 1993
To~o)
Edited by
U.lto) A. Baethmann) K.-A. Hossmann) T. Kuroiwa)
A. Marmarou) H.-J. Reulen) K. Takakura
Acta Neurochirurgica
Supplementum 60
Springer-Verlag Wien New York
Umeo Ito, M.D.
Director and Neurosurgeon in Chief, Department ofNeurosurgery, Musashino Red-Cross Hospital, Tokyo, Japan
Alexander Baethmann, M.D.
Professor, Institut für Chirurgische Forschung, Ludwig-Maximilians-Universität, München,
Federal Republic of Germany
Konstantin-A. Hossmann, M.D.
Professor, Max-Planck Institut für Neurologische Forschung, Köln, Federal Republic of Germany
Toshihiko Kuroiwa, M.D.
Associate Professor, Department ofNeuropathology, Tokyo Medical and Dental University, Tokyo, Japan
Anthony Marmarou, Ph.D.
Professor, Division of Neurosurgery, Medical College of Virginia, Richmond, Virginia, U.S.A.
Hans-J. Reulen, M.D.
Professor, Neurochirurgische Klinik, Ludwig-Maximilians-Universität, München, Federal Republic of Germany
Kintomo Takakura, M.D.
Professor, Department of Neurosurgery, Tokyo Women's Medical College, Tokyo, Japan
Proceedings of the Ninth International Symposium on Brain Edema
~
I.~
-
Organization
Honorary Member: 1. Klatzo
Organizers: U. Ito (Secretary General), K. Kogure, K. Takakura, A. Tamura, M. Tomita
Advisory Board: A. Baethmann, J. T. Hoff, K.-A. Hossmann, H. E. James, T. Kirino, T. Kuroiwa,
A. Marmarou, H.-J. Reulen, A. R. Shakhnovich
Local Organizer
Senior Members: T. Hayakawa, K. Hirakawa, H. Nagai, R. Okeda, K. Sato, Y. Shinohara, A. Terashi, T. Tsubokawa
Junior Members: N. Hayashi, J. Ikeda, Y. Ikeda, M. Ishikawa, Y. Katayama, K. Kawai, K. Nishimoto, K. Ohno,
N. Saito, T. Sasaki, T. Shigeno, R. Suzuki, K. Tanaka, H. Tomita, O. Tone, T. Yamaguchi
With 281 partly coloured Figures
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ISSN 0065-1419 (Acta Neurochirurgica/Supp1.)
ISBN-13 :978-3-7091-9336-5 e-ISBN-13 :978-3-7091-9334-1
DOI: 10.1007/978-3-7091-9334-1
Preface
The first international symposium on brain edema was held in Vienna/A ustria in 1965 followed by altogether eight
meetings since. The most recent was organized in Y okohama by the Department of Neurosurgery of the
Musashino Red Cross Hospital, Tokyo. The continuing interest of both, clinicians and experimental scientists
alike may be attributable to the fact that brain edema is a common denominator of many cerebral disorders, which
under acute conditions threatens life and weIl-being of afflicted patients. Although progress in understanding as
weIl as treatment can be recognized since 1965 many problems remain, particularly concerning the control of brain
edema under acute conditions, as in trauma or ischemia. A quantum leap was the distinction of the cytotoxic and
vasogenic brain edema prototypes as advanced by Igor Klatzo, providing for transition from a morphological to
functional understanding now. The recent brain edema meetings were certainly benefiting from developments of
both, molecular neurobiology on the one hand side and functional brain imaging at an ever-increasing resolution
on the other, such as magnetic resonance imaging orpositron emission tomography. The international symposium
in San Diego 1996 may witness further breakthroughs, hopefully also of effective treatment modalities.
The symposium in Y okohama was dedicated to the "Legacy of 28 Years of Brain Edema Research" as a
reminder of accomplishments as weIl as remaining challenges. Major guidelines were: (1) blood-parenchymal cell
border injury, (2) neuron-glial interactions and injury, (3) formation, propagation and resolution of edema, and
(4) treatment. The sessions organized around these topics were introduced by key-note lectures of internationally
high-ranking experts and frequently completed by panel sessions involving the general audience. An increasing
understanding of the complex pathophysiology, such as blood-brain barrier disruption or cell swelling and
damage, could be recognized in almost all areas which were covered. Recent emphasis is given to endothelial
factors, such as vascular/endothelial growth factor (VEGF), which is highly expressed in the fetal brain during
angiogenesis, but low in the adult brain after this process has been terminated. VEGF is considered as a
permeability factor, since embryonic brain capillaries are leaky. It may, therefore, playa role in extravasation of
brain edema around tumors, where formation of the molecule is upregulated. A continuing matter of concern is the
pathological role of mediator compounds associated with the many brain edema phenomena, such as barrier
dysfunction, cell swelling, or disturbances of the microcirculation among others. Newcomers are the vasoactive
endothelins taking part in a complex mediator network, for example by virtue to release arachidonic acid from
endothelium which in turn raises barrier permeability. Clearly, the mediator concept is useful from a clinical point
as long as results have an impact on treatment. If, however, release or activation of an ever-growing host of
mediator substances in the damaged brain cannot be therapeutically controlled due to the sheer complexity,
different approaches might be required. Major attention was also paid to the significance of neuron-glial
interactions in cell injury and edema in vivo and in vitro. Different behavior and susceptibility, respectively of
neurons and glial cells might be relevant with regard to the edematogenic role of glutamate, acidosis, hypertonic
ity, or as to the vulnerability from ischemia.
Further, most advanced technologies reaching from e.g. in situ hybridization to NMR diffusion imaging can
currently be recognized to pervade almost all scientific approaches related to the general subject. These
developments notwithstanding, basic aspects of formation, propagation, and resolution of brain edema remained
a focus of the symposium. Edema conditions studied with respect to this subject range from brain tumor to head
injury. Computerized tomography provides an important methodological basis for analysis ofthe kinetics ofbrain
edema spread and resolution in patients. Mathematical modeling for exploration of edema dynamics indicates that
both, diffusion and convection characteristics playa role as validated by MRI studies. In this context, "isotropic"
VI Preface
and "anisotropie" tissue properties can be distinguished with regard to the orientation of the nerve bundles in white
matter, which in fact is reviving former conclusions on spread of edema in relation to the fibre direction elucidated
by morphology. New data obtained on early but transient barrier opening question a major role of the vasogenic
edema type in diffuse traumatic brain injury. To the contrary, occurrence of a reduced tissue blood volume
simultaneously with an increased water content indicates significant involvement of cell swelling. The importance
of astrocytic swelling was thus extensively evaluated and discussed to reflect either uptake of extracellular
material as a result of glial clearance functions or, more likely, representing a manifestation of cytotoxic cell
damage. Treatment of brain edema continues to acquire a central position, as shown not only by the impressive
number of contributions, but also by the diversity of conditions, which were studied. The more provocative and
apparently progressive approaches of therapy were selected for a round table discussion, pro vi ding participants
with up-to-date information by experts on particularly promising modalities.
The rising attendance of scientists from all over the world and growth of oral and poster contributions
demonstrate the significance as well as well-being ofthis internationally prominent symposium. An "International
Society for Brain Edema Research" was consequently established in Y okohama in order to better focus and
structure purpose and interests for this interdisciplinary area of research. The importance to advance understand
ing of brain edema up to the molecular level and to accomplish breakthroughs for treatment, particularly for life
threatening edema manifestations were recognized as major challenges of the future. The Society sincerely
welcomes members, particularly of the younger generation, who are expected to carry on the legacy of brain
edema research into the next century. The present Proceedings are therefore dedicated to our Society, simultane
ously inviting for Brain Edema 1996 in San Diego. Finally, it is a great pleasure to gratefully acknowledge the
competent collaboration by R. Petri-Wieder of Springer, Vienna, in concluding our preparations of this volume.
Ja n uary 1994 Umeo Ito
and Coeditors
Supported by
The Commemorative Associationfor the Japan World Exposition (1970).
Contents
Cell Swelling and Cell Damage in vivo and in vitro
Klatzo, 1.: Evolution of Brain Edema Coneepts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Kempski, O. S., Volk, c.: Neuron-Glial Interaction During Injury and Edema of the CNS ............ 7
Hansson, E., Johannson, B. B., Westergren, 1., Rönnbäek, L.: Meehanisms ofGlutamate Indueed Swelling
in Astroglial Cells ...................................................................... 12
Hargreaves, R. J., Hill, R. G., Iversen, L. L.: Neuroproteetive NMDA Antagonists: the Controversy over
Their Potential for Adverse Effeets on Cortieal Neuronal Morphology ............................ 15
Staub, F., Winkler, A., Peters, J., Kempski, 0., Baethmann, A.: Meehanisms of Glial Swelling by
Araehidonie Acid ...................................................................... 20
Norenberg, M. D., Bender, A. S.: Astroeyte Swelling in Liver Failure: Role of Glutamine and Benzo-
diazepines ............................................................................ 24
Bender, A. S., Norenberg, M. D.: The Role of K+ Influx on Glutamate Indueed Astroeyte Swelling:
Effeet of Temperature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
Tomita, M., Fukuuehi, Y., Terakawa, S.: Differential Behavior of Glial and Neuronal Cells Exposed to
Hypotonie Solution .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
Mellergärd, P., Ouyang, Y.-B., Siesjö, B. K.: The Regulation of Intraeellular pH is Strongly Dependent on
Extraeellular pH in Cultured Rat Astroeytes and Neurons ...................................... 34
Akiyama, K., Yamamoto, M., Haida, M., Ohsuga, H., Shinohara, N., Shinohara, Y.: Morphologieal
Changes of Cultured Neuronal and Endothelial Cells by Human Albumin ......................... 38
Doberstein, C., Fineman, 1., Hovda, D. A., Martin, N. A., Keenly, L., Beeker, D. P.: Metabolie Alterations
Aeeompany lonic Disturbances and Cellular Swelling During a Hypoxie Insult to the Retina: an in vitro
Study ................................................................................ 41
Maxwell, W. L., Bulloek, R., Seott, A., Kuroda, Y., Graham, D. 1., Gallagher, G.: Diffuse Astroeytie
Swelling and Inereased Seeond Messenger Aetivity Following Aeute Haemophilus influenzae Meningitis -
Evidenee from a Rat Model .............................................................. 45
Mediator Mechanisms in Vasogenic and Cytotoxic Brain Edema
Schürer, L., Corvin, S., Röhrieh, F., Abels, c., Baethmann, A.: LeukoeytelEndothelial Interactions and
Blood-Brain Barrier Permeability in Rats During Cerebral Superfusion with L TB 51
4 ••••••••••••••.•••
Nagashima, T., Shigin, W., Mizoguehi, A., Arakawa, M., Yamaguehi, M., Tamaki, N.: The Effeet of
Leukotriene C4 on the Permeability of Brain Capillary Endothelial Cell Monolayer ................. 55
Espanol, M. T., Xu, Y., Litt, L., Chang, L.-H., James, T. L., Weinstein, P. R., Chan, P. H.: Modulation of
Edema by Dizoeilpine, Kynurenate, and NBQX in Respiring Brain Slices After Exposure to Glutamate. 58
VIII Contents
Kuchiwaki, H., Inao, S., Yamamoto, M., Yoshida, K., Sugita, K.: An Assessment of Progression of Brain
Edema with Amino Acid Levels in Cerebrospinal Fluid and Changes in Electroencephalogram in an Adult
Cat Model of Cold Brain Injury ........................................................... 62
Sharma, H. S., Westman, J., Nyberg, F., Cervos-Navarro, J., Dey, P. K.: Role of Serotonin and Prostaglan-
dins in Brain Edema Induced by Heat Stress. An Experimental Study in the Y oung Rat .............. 65
Stanimirovic, D. B., Bertrand, N., McCarron, R., Uematsu, S., Spatz, M.: Arachidonic Acid Release and
Permeability Changes Induced by Endothelins in Human Cerebromicrovascular Endothelium ......... 71
Joo, F., Kovacs, J., Szerdahelyi, P., Temesvari, P., Tosaki, A..: The Role of Histamine in Brain Oedema
Formation ............................................................................ 76
Schilling, L., Wahl, M.: Effects of Antihistaminics on Experimental Brain Edema . . . . . . . . . . . . . . . . . . . 79
Yamada, E., Chue, C. H., Yukioka, N., Hazama, F.: Causative Role of Lysosomal Enzymes in the
Pathogenesis of Cerebral Lesions Due to Brain Edema Under Chronic Hypertension . . . . . . . . . . . . . . . . . 83
Nishino, A., Suzuki, M., Yoshimoto, T., Otani, H., Nagura, H.: A Novel Aspect ofThrombin in the Tissue
Reaction Following Central Nervous System Injury ........................................... 86
Judy, K. D., Bulkley, G. B., Hedlund, B. E., Long, D. M.: Proposed Toxic Oxidant Inhibitors Fail to Reduce
Brain Edema .......................................................................... 89
Ikeda, J., Ma, L., Morita, 1., Murota, S.: Involvement of Nitric Oxide and Free Radical (02-) in Neuronal
Injury Induced by Deprivation of Oxygen and Glucose in vitro .................................. 94
Rap, Z. M., Schoner, W., Czemicki, Z., Hildebrandt, G., Mueller, H. W., Hoffmann, 0.: The Endogenous
Ouabain-Like Sodium Pump Inhibitor in Cold Injury-Induced Brain Edema . . . . . . . . . . . . . . . . . . . . . . . . 98
Go, K. G., Zuiderveen, F., De Ley, L., Ter Haar, J. G., Parente, L., Solito, E., Molenaar, W. M.: Effect of
Steroids on Brain Lipocortin Immunoreactivity .............................................. 101
Minamikawa, J., Kikuchi, H., Ishikawa, M., Yamamura, K., Kanashiro, M.: The Effects of Atrial Natriuretic
Peptide on Brain Edema, Intracranial Pressure and Cerebral Energy Metabolism in Rat Congenital
Hydrocephalus ........................................................................ 104
Blood-Brain Barrier Function
Risau, W.: Molecular Biology of Blood-Brain Barrier Ontogenesis and Function . . . . . . . . . . . . . . . . . . .. 109
Johshita, H., Asano, T., Matsui, T., Koide, T.: Effects of Protein Kinase C Activators on Na, K-ATPase
Activity in Rat Brain Microvessels ........................................................ 113
Sato, S., Suga, S., Yunoki, K., Mihara, B.: Effect of Barrier Opening on Brain Edema in Human Brain
Tumors .............................................................................. 116
Ikeda, Y., Wang, M., Nakazawa, S.: Simple Quantitative Evaluation of Blood-Brain Barrier Disruption in
Vasogenic Brain Edema ................................................................. 119
Fukuhara, T., Gotoh, M., Kawauchi, M., Asari, S., Ohmoto, T., Tsutsui, K., Shohmori, T.: Detection of
Endogenous Albumin as an Index of Blood Parenchymal Border Alteration ......... _. . . . . . . . . . . . .. 121
Westergren, 1., Nyström, B., Hamberger, A., Johansson, B. B.: Amino Acids in Extracellular Fluid in
Vasogenic Brain Edema ................................................................. 124
Johansson, B. B., Westergren, 1.: Pharmacological Reduction of Brain Edema Induced by Intracarotid
Infusion of Protamine Sulphate: a Comparison Between a Free Radical Scavenger and an AM PA Receptor
Antagonist ............................................................................ 128
Gumerlock, M. K., York, D., Durkis, D.: Visual Evoked Responses as a Monitor of Intracranial Pressure
During Hyperosmolar Blood-Brain Barrier Disruption ......................................... 132
Contents IX
Ikeda, Y., Toda, S., Wang, M., Nakazawa, S.: Early Changes of Blood-Brain Barrier and Superoxide
Seavenging Aetivity in Rat Cryogenie Brain Injury ........................................... 136
Lafuente, J. V., Cerv6s-Navarro, J., Gutierrez Argandofia, E.: Evaluation of BBB Damage in an VV
Irradiation Model by Endogenous Protein Traeers ............................................ 139
Ijima, T., Kubota, Y., Kuroiwa, T., Sankawa, H.: Blood-Brain Barrier Opening Following Transient Reflex
Sympathetie Hypertension ............................................................... 142
Formation, Propagation and Resolution of Brain Edema
Cerv6s-Navarro, J., Türker, T., Worthmann, F.: Morphology of Non-Vaseular Intraeerebral Fluid Spaees 147
Cerv6s-Navarro, J., Lafuente, J. V., Gutierrez, E., Kannuki, S.: Subeortieal V-Fibers Layer Preservation in
Brain Edema .......................................................................... 151
Kuroiwa, T., Veki, M., Chen, Q., Iehinose, S., Okeda, R.: Is the Swelling in Brain Edema Isotropie or
Anisotropie? .......................................................................... 155
Kuroiwa, T., Veki, M., Chen, Q, Suemasu, H., Taniguehi, I., Okeda, R.: Biomeehanieal Charaeteristies of
Brain Edema: the Differenee Between Vasogenie-Type and Cytotoxie-Type Edema ................. 158
Kadota, E., Nonaka, K., Karasuno, M., Nishil, K., Nakamura, Y., Namikawa, K., Okazaki, Y., Teramura,
K., Hashimoto, S.: Experimental Quantitative Evaluation of Transvaseular Removal of Vnneeessary
Substanees in Brain Edema Fluid. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 162
Nagashima, T., Tamaki, N., Takada, M., Tada, Y.: Formation and Resolution of Brain Edema Assoeiated
with Brain Tumors. A Comprehensive Theoretieal Model and Clinieal Analysis .................... 165
Maeda, M., Takaehi, T., N akai, M., Krieger, A. J., Sapru, H. N.: Medullary Cardiovaseular Center and Aeute
Brain Swelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 168
Maeda, M., Nakai, M., Krieger, A. J., Sapru, H. N.: Dysfunetion of the Medullary Cardiovaseular Center
May Cause Aeute Spinal Cord Swelling .................................................... 171
Pliusheheva, N., Shakhnovieh, A.: CSF Dynamies in Patients with Meningiomas ................... 174
Ischemic Brain Edema: Pathophysiology and Nuclear Magnetic Resonance
Jolesz, F. A.: Compartmental Analysis of Brain Edema Vsing Magnetie Resonanee Imaging .......... 179
Chambers, I. R., Choksey, M. S., Clark, A., Green, A., Jenkins, A., Mendelow, A. D.: AThermal Clearanee
Probe for Continuous Monitoring of Cerebral Blood Flow .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 184
Choksey, M. S., Chambers, I. R., Mendelow, A. D., Jenkins, A., Sengupta, R. P.: Measurement of in vivo
Cortieal Thermal Clearanee in Man During Complete Cireulatory Standstill ....................... 187
Yamaguehi, M., Wu, S., Ehara, K., Nagashima, T., Tamaki, N.: Cerebral Blood Flow ofRats with Water-
Intoxieated Brain Edema ................................................................ 190
Fujisawa, H., Maxwell, W. L., Graham, D. I., Reasdale, G. M., Bulloek, R.: Foeal Mierovaseular Oeclusion
After Aeute Subdural Haematoma in the Rat: a Meehanism for Isehaemie Damage and Brain Swelling? 193
Hata, R., Matsumoto, M., Yamamoto, K., Ohtsuki, T., Ogawa, S., Handa, N., Kubo, T., Matsunaga, T.,
Nishimura, T., Kamada, T.: An Isehemie Opening of the Blood-Brain Barrier May Deteriorate
Brain Stern Auditory Evoked Potentials Following Transient Hindbrain Isehemia in Gerbils . . . . . . . . . .. 197
Yamaguehi, M., Sugimaehi, K., Nakano, K., Fujimoto, M., Takahashi, M., Chikugo, T., Ogawa, H.:
Memory Defieit Aeeompanying Cerebral Neurodegeneration After Stroke in Stroke-Prone Spontaneously
Hypertensive Rats (SHRSP) .............................................................. 200
x Contents
Ting, P., Wang, P., Song, H., Xu, S.: Neuro-Pathophysio-Biochemical Profiles of Neonatal Asphyxia . .. 203
Jones, S. C., Perez-Trepichio, A. D., Xue, M., Furlan, A. J., Awad, I. A.: Magnetic Resonance Diffusion
Weighted Imaging: Sensitivity and Apparent Diffusion Constant in Stroke . . . . . . . . . . . . . . . . . . . . . . . .. 207
Vexler, Z. S., Roberts, T. P. L., Derugin, N., Kozniewska, E., Arieff, A. 1., Kucharcyk, J.: Mechanisms of
Brain Injury Associated with Partial and Complete Occlusion of the MCA in Cat ................... 211
Kajima, T., Azuma, K., Itoh, K., Kagawa, R., Yamane, K., Okada, Y., Shima, T.: Diffusion Anisotropy of
Cerebra I Ischemia ...................................................................... 216
Allen, K. L., Busza, A. L., Williams, S. C. R.: A Sodium Magnetic Resonance Imaging Study of Acute
Cerebral Ischaemia in the Gerbil .......................................................... 220
Takahashi, M., Fritz-Zieroth, B., Chikugo, T., Ogawa, H.: In vivo Differentiation of Edematous Changes
After Stroke in Spontaneously Hypertensive Rats Using Diffusion Weighted MRI .................. 224
Kobayashi, H., Ide, H., Kodera, T., Handa, Y., Kabuto, M., Kubota, T., Maeda, M.: Effect of Mannitol on
Focal Cerebral Ischemia Evaluated by Magnetic Resonance Imaging ............................. 228
Ischemic Brain Edema: Pathobiochemistry and Brain Edema
Hallenbeck, J. M.: Blood-Damaged Tissue Interaction in Experimental Brain Ischemia . . . . . . . . . . . . . .. 233
Ishii, H., Bertrand, N., Stanimirovic, D., Strasser, A., Mrsulja, B. B., Spatz, M.: The Relationship Between
Cerebral Ischemic Edema and Monoamines: Revisited . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 238
Katayama, Y., Kawamata, T., Maeda, T., Tsubokawa, T.: Free Fatty Acid Liberation and Cellular Swelling
During Cerebral Ischemia: the Role of Excitatory Amino Acids ................................. 242
Vexler, Z. S., Roberts, T. P. L., Kucharczyk, J., Arieff, A. 1.: Severe Brain Edema Associated with
Cumulative Effects of Hyponatremic Encephalopathy and Ischemic Hypoxia . . . . . . . . . . . . . . . . . . . . . .. 246
Fukuhara, T., Gotoh, M., Kawauchi, M., Asari, S., Ohmoto, T.: Endogenous Superoxide Dismutase Activity
in Reperfusion Injuries .................................................................. 250
Ting, P., Xu, S., Krumins, S.: Endogenous Opioid System Activity Following Temporary Focal Cerebral
Ischemia ............................................................................. 253
Samoto, K., Ikezaki, K., Yokoyama, N., Fukui, M.: P-Glycoprotein Expression in Brain Capillary Endo-
thelial Cells After Focal Ischemia in Rat .................................................... 257
Yamada, K., Sakaguchi, T., Yuguchi, T., Kohmura, E., Otsuki, H., Koyama, T., Hayakawa, T.: Blood-Bome
Macromolecule Induces FGF Receptor Gene Expression After Focal Ischemia ..................... 261
Yamada, E., Kataoka, H., Chue, C.-H., Hazama, F.: Expression of Basic Fibroblast Growth Factor in
Astrocytes at the Site of Cerebral Lesions and Edematous Areas Under Chronic Hypertension ......... 265
Kawamata, T., Katayama, Y., Kinoshita, K., Yoshino, A., Hirota, H., Tsubokawa, T.: Cytochrome Oxidase
and Hexokinase Activities in an Infusion Edema Model with Preserved Blood Flow ................. 268
Shima, K., Ohashi, K., Umezawa, H., Chigasaki, H., Okuyama, S.: Blood-Brain Barrier, Cerebral Blood
Flow, and Brain Edema in Spontaneously Hypertensive Rats with Chronic Focal Ischemia .......... " 271
Mossakowski, M. J., Lossinsky, A. S., Pluta, R., Wisniewski, H. M.: Abnorrnalities of the Blood-Brain
Barrier in Global Cerebral Ischemia in Rats Due to Experimental Cardiac Arrest. . . . . . . . . . . . . . . . . . .. 274
Ischemic Brain Edema: Treatment
Park, C. K., McCulloch, J., Jung, D. S., Kang, J. K., Choi, C. R.: Do N-methyl-D-aspartate Antagonists
Have Disproportionately Greater Effects on Brain Swelling than on Ischemic Damage in Focal Cerebra I
Infarction? ............................................................................ 279