Cover -- Half-title -- Title -- Copyright -- Contents -- Contributors -- Preface -- Acknowledgments -- Major contributors -- Part I Special lectures -- 1 Zinc toxicity in the ischemic brain -- REFERENCES -- 2 Central nervous system ischemia: diversity among the caspases -- Introduction -- Global ischemia -- Focal ischemia -- Neonatal hypoxic-ischemic brain injury -- Spinal cord ischemia -- Conclusion -- Acknowledgments -- REFERENCES -- Part II Oxidative stress -- 3 Peroxynitrite and injury to the vasculature and central nervous system in stroke and neurodegeneration -- Introduction -- Oxygen toxicity and superoxide -- Superoxide and stroke -- SOD and the scavenging of superoxide -- Nitric oxide and peroxynitrite -- Tyrosine nitration -- Nitration of prostacyclin synthase -- Nitration of structural proteins -- SOD and motor neuron degeneration in ALS -- Concluding remarks -- REFERENCES -- 4 Interaction between inducible nitric oxide and cyclooxygenase-2 in ischemic brain injury -- Introduction -- Neuromodulatory and neurotoxic actions of nitric oxide -- NO and ischemic brain injury -- iNOS and ischemic brain injury -- COX gene expression and inflammation -- COX-2 and cerebral ischemia -- Interaction between iNOS-derived NO and COX-2 -- Conclusion -- Acknowledgments -- REFERENCES -- 5 Mechanisms of ischemic tolerance -- Introduction -- Changes in protein expression after preconditioning events -- Mechanisms of ischemic tolerance -- Nitric oxide (NO) -- p21 -- Extracellular-signal-regulated kinases (Erks) -- Alternate activators of neuronal preconditioning -- Conclusion -- Acknowledgments -- REFERENCES -- 6 Clinically tolerated NMDA receptor antagonists and newly cloned NMDA receptor subunits that mimic them -- Excitotoxic and free radical injury to cerebrocortical neurons.

Therapeutic approaches to preventing cerebrocortical neuron injury: glutamate receptor antagonists -- NMDA receptor antagonists: open-channel block and S-nitrosylation -- A new family of NMDA receptor subunits that act as modulatory agents -- Events downstream to the NMDA receptor -- Conclusions and future perspectives -- REFERENCES -- Part III Apoptosis -- 7 Cell death programs in neural development and disease -- REFERENCES -- 8 Apoptotic gene expression in brain ischemia and ischemic tolerance -- Introduction -- Anti-apoptotic gene expression in ischemia and tolerance are not cell-type specific -- Apoptotic gene expression in ischemia and tolerance are not regionally specific -- Apoptotic gene expression in ischemia and tolerance are not injury-type specific -- Apoptotic gene expression in ischemia (and perhaps tolerance) is not protein specific -- REFERENCES -- 9 Cellular mechanisms of white matter ischemia: what can we learn from culture models? -- Introduction -- Cell culture approaches to white matter injury -- Advantages and disadvantages of cell culture approaches -- Assessing cellular injury in culture models -- Vulnerability of individual white matter components -- Axons -- Oligodendrocytes -- Astrocytes -- Microglia -- Endothelial cells -- Putting white matter back together: studying cellular interactions in culture -- Beyond cell culture -- Acknowledgments -- REFERENCES -- Part IV Hot topics -- 10 Astrocytes in ischemic stroke -- Astrocytes are active participants in brain function -- Astrocytes have traditionally received little attention in the stroke field -- The excitotoxin hypothesis revised -- Definition of spreading depression -- Spreading depression is spontaneously evoked in focal stroke and head injury -- Spreading depression increases lesion size -- Spreading depression evokes a widespread inflammatory response.

Astrocytic calcium signaling as a tool to study spreading depression -- Astrocytic gap junctions propagate or amplify ischemic injury -- Conclusion -- Acknowledgment -- REFERENCES -- 11 Aquaporin-4 water channels and brain edema -- Introduction -- Methods -- Transgenic mice -- Water intoxication -- Electron microscopy -- Tissue-specific gravity -- Permanent focal cerebral ischemia -- Statistical analysis -- Results -- Discussion -- Acknowledgments -- REFERENCES -- 12 Neuroprotection with tetracyclines in brain ischemia models -- Introduction -- Protection in a global ischemia model -- Protection in a focal brain ischemia model -- Protection in a cell culture model -- Conclusion -- REFERENCES -- 13 Spreading depression: a teleological means for self-protection from brain ischemia -- Introduction -- Ischemic tolerance -- Spreading depression -- SD and gap junctions -- HOTCs, SD and Cai2+ -- Conclusion -- Acknowledgments -- REFERENCES -- Part V Hemorrhage, edema, and secondary injury -- 14 The role of matrix metalloproteinases and urokinase in blood-brain barrier damage with thrombolysis -- Introduction -- Methods -- MCAO and the BBB -- Zymography -- Cell cultures -- Statistical analysis -- Results -- Sucrose space -- MMPs -- Cell cultures -- Discussion -- Conclusion -- Acknowledgments -- REFERENCES -- 15 Does brain nitric oxide generation influence tissue oxygenation after severe human subarachnoid hemorrhage? -- Introduction -- Patients and methods -- Patients -- Neurochemical monitoring -- Nitrite and nitrate measurements -- Endothelin-1 measurements -- Data collection and statistical analysis -- Results -- Dialysate NO measurements -- Endothelin-1 in CSF and microdialysate -- Correlation between NO metabolites, brain tissue oxygen and metabolism -- Discussion -- Conclusion -- Acknowledgments -- REFERENCES.

16 Tissue plasminogen activator and hemorrhagic brain injury -- Effects of tissue-type plasminogen activator in acute clinical stroke -- Effects of tPA in experimental cerebral ischemia -- tPA amplifies neuronal damage in vitro -- tPA induces hemorrhage in a rat model of embolic focal ischemia -- Alpha-phenyl-tert-butyl-nitrone reduces tPA-induced hemorrhage and brain injury -- Magnetic resonance markers of tPA-induced hemorrhage -- Conclusion -- Acknowledgments -- REFERENCES -- 17 Dynamics of infarct evolution after permanent and transient focal brain ischemia in mice -- Introduction -- Material and methods -- Production of focal brain ischemia -- Brain imaging -- Statistics -- Results -- Permanent MCA thread occlusion -- Brain metabolism -- Genomic expressions -- TUNEL -- Transient MCA thread occlusion -- Brain metabolism -- Genomic expression -- TUNEL -- Thrombolysis of MCA clot embolism -- Blood reperfusion -- Brain metabolism -- TUNEL -- Discussion -- Conclusion -- REFERENCES -- Part VI Inflammation -- 18 Inflammation and stroke: benefits or harm? -- Introduction -- Expression of inflammatory cytokines and chemokines after ischemic brain injury -- Expression of inflammatory cytokines in brain ischemic tolerance -- Role of inflammatory cytokines and chemokines in ischemic brain injury -- Role of adhesion molecules in ischemic brain injury -- Anti-inflammatory strategies in stroke -- Conclusion -- REFERENCES -- 19 TNF-alpha and ceramide are involved in the mediation of neuronal tolerance to brain ischemia -- Introduction -- Methods -- Cortical neuronal cultures -- Hypoxic pretreatment -- Severe hypoxic treatment -- Pretreatment of neuronal cultures with TNF-Alpha and C-2 ceramide and blocking reagents -- Quantitation of neuronal injury -- Intracellular ceramide levels -- Measurements of TNF-Alpha concentrations -- Statistical analysis -- Results.

Description of the in vitro model of hypoxia tolerance -- TNF-Alpha as a mediator of hypoxic preconditioning of neurons -- Ceramide is a downstream mediator of hypoxic tolerance -- Discussion -- REFERENCES -- 20 Sites and mechanisms of IL-1 action in ischemic and excitotoxic brain damage -- Cytokines and ischemic brain damage -- IL-1 expression in stroke -- Evidence for IL-1 involvement in stroke -- Mechanisms of IL-1 action -- Specific sites of IL-1 action -- Involvement of the hypothalamus in IL-1 actions -- Acknowledgments -- REFERENCES -- 21 Protease generation, inflammation and cerebral microvascular activation -- Introduction -- The microvascular basal lamina and ECM -- Endothelial cell-astrocyte-neuron interrelationships -- Focal cerebral ischemia and microvascular responses -- Markers of neuron injury -- The microvascular basal lamina and integrin receptors -- Causes of matrix degradation during MCAO -- Microvascular activation after MCAO -- Rapid microvascular activation and cellular inflammation -- Conclusion -- Acknowledgments -- REFERENCES -- Part VII Gene transfer and therapy -- 22 Adenoviral vectors for gene therapy in stroke -- Introduction -- The adenovirus -- Delivery of adenoviral vectors to the brain -- Intravascular -- Intraventricular -- Intraparenchymal -- Delivery through peripheral nerves -- Measurement and timing of therapeutic gene expression -- Therapeutic genes in stroke -- REFERENCES -- 23 Gene transfer of glial cell line-derived neurotrophic factor prevents ischemic brain injury -- Topical application of glial cell line-derived neurotrophic factor reduces ischemic brain injury after permanent middle… -- Effect of adenovirus-mediated gene transfer of GDNF on ischemic brain injury -- Acknowledgments -- REFERENCES -- 24 Vasomotor effects of nitric oxide, superoxide dismutases and calcitonin gene-related peptide.

Introduction.