Approximately half a million Americans suffer brain ischemic episodes every year. These brain strokes are the third leading cause of death in the United States and the number-one cause of permanent disability. Over the past decade, we have made extensive attempts to understand the biological mechanisms that underlie stroke-induced neuronal injury. This research has been benefited by the introduction of a variety of new technologies and assays aimed at deciphering the complex neuronal degenerating processes triggered by cerebral vascular disorders or other neurological diseases that produce ischemic episodes. New Concepts in Cerebral Ischemia presents techniques and theories for understanding the various stages of early pathogenesis in order to design specific strategies to protect neurons from further injury. Short, specific, and comprehensive chapters provide detailed descriptions of the new methods employed in both basic and clinical research that are revolutionizing the field of ischemia research. Written by international experts in CNS dysfunction, the book includes methods to elucidate the pathogenesis of ischemia, technologies used in the design of specific strategies to protect neurons from further injury, and new approaches to treat patients with acute ischemic episodes. With this book, you will gain new insights not only into cerebral vascular research, but also into neurological disease in general.
Author(s): Rick C. S. Lin
Series: Frontiers in Neuroscience
Edition: 1
Publisher: CRC Press
Year: 2001
Language: English
Pages: 318
Table of Contents......Page 0
NEW CONCEPTS IN CEREBRAL ISCHEMIA......Page 1
Methods & New Frontiers in Neuroscience......Page 3
Preface......Page 4
The Editor......Page 6
Contributors......Page 7
Contents......Page 9
CONTENTS......Page 11
I.2 INTRODUCTION......Page 12
1.3.1 ISCHEMIC STROKE......Page 13
1.4.1 EFFECTS OF OVARIECTOMY......Page 15
1.4.2 EFFECTS OF ESTROGEN REPLACEMENT......Page 16
1.5.1 CEREBRAL BLOOD FLOW CHANGES......Page 17
1.5.2 VASCULAR NITRIC OXIDE FORMATION......Page 19
1.5.5 ANTIOXIDANT EFFECTS......Page 21
1.5.7 PROTECTION AGAINST GLUTAMATE-INDUCED EXCITOTOXICITY......Page 26
1.5.8 ACTIVATION OF MAP KINASE PATHWAYS......Page 27
1.5.9 UPREGULATION OF BCL-2 EXPRESSION......Page 28
1.6 GENOMIC VS. NONGENOMIC MECHANISMS OF ESTROGEN NEUROPROTECTION......Page 29
REFERENCES......Page 31
CONTENTS......Page 41
2.1 INTRODUCTION......Page 42
2.2.1.1.1 Pattern of Injury in Human Infants......Page 43
2.2.1.1.3.2 Acute Asphyxia in Piglets......Page 44
2.2.1.2.2.1 Partial Prolonged Asphyxia in Monkeys......Page 46
2.2.1.3.1 Injury in Human Infants......Page 47
2.2.1.4 Syndrome of Hypoxic-Ischemic Encephalopathy (HIE)......Page 48
2.2.2.1.1 Injury in Human Neonates......Page 49
2.2.2.2 Periventricular Leukomalacia (PVL)......Page 50
2.2.2.3.1 Insult in Human Neonates......Page 51
2.2.2.3.2 Models of Brain Injury from Hypothermic Circulatory Arrest......Page 52
2.3.1 EXCITOTOXIC MECHANISMS......Page 53
2.3.2 THE NEUROTOXIC CASCADE AND DELAYED ENERGY FAILURE......Page 54
2.3.3 THE APOPTOSIS-NECROSIS CONTINUUM......Page 55
2.3.4.1 Hypothermia......Page 57
2.3.4.3 Carbon Dioxide and Acidosis......Page 58
2.3.4.6 Caspase Inhibition......Page 59
2.3.4.9 Hypoxic Preconditioning......Page 60
REFERENCES......Page 61
3.1 HYPOXIC-ISCHEMIC BRAIN INJURY AS A MAJOR CNS DISORDER......Page 71
3.2 THERAPEUTIC POTENTIALS OF NEURAL STEM CELLS......Page 72
3.3 THE NEURAL STEM CELL RESPONSE TO HYPOXICISCHEMIC INJURY......Page 73
3.4 COMBINING CELL REPLACEMENT WITH GENE THERAPY VIA NEURAL STEM CELLS......Page 78
3.5 THE ATTEMPT OF SELF-REPAIR IN THE INJURED MAMMALIAN BRAIN......Page 79
3.6 TRANSLATING STEM CELL BIOLOGY INTO THERAPY......Page 81
3.7 APPLICATION OF BIODEGRADABLE SYNTHETIC POLYMER TO NEURAL STEM CELLS......Page 82
REFERENCES......Page 84
CONTENTS......Page 88
4.2.1 BACKGROUND......Page 89
4.2.2 CA2+-MEDIATED FAST EXCITOTOXICITY......Page 90
4.2.3.1 Calpains......Page 91
4.2.3.3 Ca2+-Dependent Protein Kinases......Page 92
4.2.3.5 Nuclear Factor Kappa B......Page 93
4.2.3.7 Oncosis vs. Apoptosis......Page 94
4.3.1 BACKGROUND......Page 95
4.3.2.1 Free Radical Production in Mitochondria......Page 96
4.3.2.3 ROS Production by Transition Metals......Page 97
4.3.2.5 Metabolism of Arachidonic Acid......Page 98
4.4.1 BACKGROUND......Page 99
4.4.2.1 pH......Page 100
4.4.2.3 Fas Receptor......Page 101
4.4.3.2 The Proapoptotic Family of Bcl-2......Page 102
4.4.3.4 Reevaluation of Ischemic Neuronal Apoptosis......Page 103
4.5 MAXIMIZATION FOR PREVENTION OF HYPOXICISCHEMIC NEURONAL DEATH......Page 104
4.7 ACKNOWLEDGMENTS......Page 105
REFERENCES......Page 106
5.1 INTRODUCTION......Page 122
5.2 RAPID NEURONAL DEATH AND SECONDARY CA2+ RESPONSES......Page 123
5.3.1 DELAYED INCREASES IN INTRACELLULAR CA2+......Page 130
5.3.2 APOPTOSIS......Page 131
5.3.3 CHRONIC DEPRESSION OF INTRACELLULAR CA2+ SIGNALING......Page 132
5.4 CONCLUSION......Page 137
REFERENCES......Page 138
6.1 INTRODUCTION......Page 145
6.3 IN VIVO SOURCES FOR TOXIC ZINC ACCUMULATION: VESICULAR AND NONVESICULAR......Page 146
6.4 ROUTES OF ZINC ENTRY......Page 147
6.5 INTRACELLULAR SIGNALING EVENTS MEDIATING ZINC TOXICITY......Page 148
6.6 AN EFFECTOR MECHANISM OF ZINC TOXICITY: OXIDATIVE STRESS......Page 150
6.8 ANOTHER EFFECTOR MECHANISM OF ZINC TOXICITY: P75NTR/NADE-MEDIATED APOPTOSIS......Page 151
6.9 PROTECTIVE MEASURES AGAINST ZINC TOXICITY......Page 153
6.10 SUMMARY......Page 154
REFERENCES......Page 155
7.1 SPHERES OF ACTION......Page 161
7.2. INTRODUCTION......Page 162
7.3. PATHOLOGY OF STROKE......Page 163
7.4 ADENOSINE RELEASE DURING ISCHEMIA......Page 164
7.6 DISEASE AND DRUG-INDUCED ADENOSINE RECEPTOR FLUCTUATIONS......Page 165
7.7 ADENOSINE ACTIONS DURING CEREBRAL ISCHEMIA......Page 167
7.8 INDIRECT EFFECTS OF ADENOSINE AND STROKE......Page 171
7.9 ADENOSINE AND THE TREATMENT OF ISCHEMIC STROKE......Page 172
7.10 CONCLUSION......Page 174
REFERENCES......Page 176
8.1 TWO DIFFERENT FORMS OF NEURONAL CELL DEATH: APOPTOSIS AND ONCOSIS......Page 190
8.3 ACTIVATION OF CALPAIN 1 AND 2 IN ONCOTIC DEATH......Page 191
8.4 CASPASE CASCADE IN APOPTOSIS......Page 192
8.6.1 CASPASE-3 AND CALPAIN 1 AND 2 SHARE MANY COMMON OR RELATED SUBSTRATES......Page 194
8.7 CALPAIN-CASPASE CROSSTALK......Page 199
REFERENCES......Page 201
CONTENTS......Page 210
9.2.1 STROKE: HOW IMPORTANT IS IT?......Page 211
9.2.2 STROKE: ITS PATHOPHYSIOLOGY......Page 212
9.3 THE BRAIN INFLAMMATORY RESPONSE TO INJURY......Page 216
9.4 TNFalpha IN STROKE AND BRAIN INJURY......Page 218
9.5 IL-1beta IN STROKE AND BRAIN INJURY......Page 219
9.7 NEURODESTRUCTIVE AND NEUROPROTECTIVE GENE EXPRESSION FOLLOWING STROKE......Page 222
9.8 STRATEGIES TO TARGET STROKE: BRAIN INFLAMMATION AND ITS COMPLEXITIES......Page 223
9.9.1 BLOCKING CYTOKINE ACTIONS......Page 224
9.9.2 ANTI-ADHESION MOLECULE ANTIBODIES......Page 227
9.10.1 CAMP AND PKC......Page 228
9.10.2 P38 MITOGEN-ACTIVATED PROTEIN KINASE ACTIVATION AND INHIBITION IN STROKE......Page 229
9.10.3 CSAIDS (P38 INHIBITORS)......Page 230
9.10.5 P38 MAPK INHIBITION ON BRAIN INJURY, DOWNSTREAM SIGNALING, AND INFLAMMATORY CYTOKINE EXPRESSION POST-STROKE......Page 231
9.10.6 SB 239063 EFFECTS DEVELOPMENT AND RESOLUTION OF INFARCT POST-STROKE......Page 233
9.10.7 SB 239063 NEUROPROTECTION FOLLOWING IN VITRO ISCHEMIA......Page 234
9.11 SUMMARY AND CONCLUSIONS......Page 237
REFERENCES......Page 240
10.1 PATHOPHYSIOLOGY OF CEREBRAL ISCHEMIA......Page 256
10.1.1.1 No-Reflow Phenomenon......Page 257
10.1.1.2 Postischemic Hypoperfusion......Page 258
10.1.2 HYPOXIA AND HYPOGLYCEMIA......Page 259
10.1.3.1 Free Radicals......Page 260
10.1.3.2 Microcirculation......Page 261
10.2 HYPERBARIC OXYGEN......Page 262
10.2.1.2 Dalton’s Law......Page 263
10.2.2.1 PMNL — Endothelial Adherence......Page 264
10.2.2.2 Free Radicals......Page 266
10.2.3 HUMAN STUDIES AND CONCLUSIONS......Page 267
REFERENCES......Page 270
11.1 INTRODUCTION......Page 274
11.2 MODELS OF ISCHEMIC TOLERANCE......Page 275
11.2.1 IN VIVO GLOBAL AND FOCAL ISCHEMIA MODELS......Page 276
11.2.3 THE 3-NITROPROPRIONIC ACID CHEMICAL PRECONDITIONING MODEL......Page 277
11.2.4 OTHER MODELS......Page 278
11.4. GLUTAMATE AND RECEPTORS......Page 279
11.5. STRESS PROTEINS......Page 283
11.6 PROTEIN SYNTHESIS......Page 290
11.7 BCL-2 RELATED GENE EXPRESSION......Page 291
11.8 STRUCTURAL PROTEIN DEGRADATION......Page 294
11.9. ADENOSINE AND RECEPTORS......Page 298
11.10.1 INTERLEUKIN-1......Page 303
11.10.2 TUMOR NECROSIS FACTOR-alpha......Page 304
11.10.3 GLIA......Page 305
11.11 CONCLUSIONS......Page 306
REFERENCES......Page 307
