Preface; Contents; Contributors; Part I: Stroke Neuroprotection: The History and Learning Experience; Chapter 1: Reflections on€Neuroprotection Research and€the€Path Toward Clinical Success; 1 Introduction: A€Brief Chronological History of€Stroke; 1.1 Of Neurons and€Time; 1.1.1 Extrapolated Stroke and€Cerebrovascular Disease Incidence; 1.1.2 Time-brain matters!; 2 Limited Benefit Treatment Options for€Acute Ischemic Stroke Victims: Successes!; 2.1 Thrombolysis: Thrombolytic Therapy; 2.2 Endovascular Procedures and€Thrombolysis; 2.2.1 ESCAPE [32]: Table 1.3; 2.2.2 EXTEND-IA [33]: Table 1.4.

2.2.3 MR CLEAN [31]: Table 1.52.2.4 REVASCAT [34]: Table 1.6; 2.2.5 SWIFT-PRIME [35]: Table 1.7; 2.2.6 Endovascular Procedure Benefit; 2.3 Embolectomy Concerns; 2.3.1 Patient Population Selection for€Embolectomy and€Thrombolysis; 2.3.2 Limitations of€the€Trials; Patient Selection Bias; Saving Penumbra; Time to€Treatment; Coadministration of€Thrombolytics; 2.3.3 Future of€Embolectomy; Endovascular Procedure Summary; 3 Neuroprotection; 3.1 Evolving Opportunities; 3.2 The RIGORs of€Drug Development: Guideline Adherence; 3.3 Meta-analysis of€Translational Studies; 4 Comorbidities and€Models.

2.4 Providing Potential Explanations for€Discrepancies Between€Preclinical and€Clinical Trial Results2.5 Informing Clinical Trial Design; 3 Limitations of€Systematic Review and€Meta-analysis; 4 Future of€Preclinical Systematic Review and€Meta-analysis; 5 Conclusions; 6 Resources; References; Chapter 3: Neuroprotection Is Technology, Not Science; 1 Introduction; 2 Part 1: Physics and€Biology; 2.1 A Tale of€Two Cultures; 2.2 What Is Measured?; 2.3 The Mathematizing of€Biology; 3 Part 2: A€Theory of€Acute Cell Injury; 3.1 Introduction to€the€Theory; 3.2 Qualitative Description of€the€Theory.

3.3 The Autonomous Theory3.4 Solutions of€the€Autonomous Theory; 3.5 Monostable Outcome; 3.6 Bistable Outcome; 3.7 Pre-treatment Therapies; 3.8 Closed Trajectories and€the€Autonomous Theory; 4 Technological Applications; 4.1 Approaches to€Therapy; 4.2 Ascertaining Injury Intensity; 4.3 Protective Therapeutics; 4.4 The Non-autonomous Dynamical Theory of€Acute Cell Injury; 4.5 Sequential Injuries; 4.6 Solutions of€the€Multiple Injury Model; 4.6.1 Preconditioning; 4.6.2 Post-injury Drug Treatment; 4.7 Spatial Applications; 4.8 A Possible Neuroprotective Technology.

4.1 Hypertension Models4.2 Diabetic Models; 4.2.1 Coadministration of€Drugs in€Stroke Models; 5 Drug Development Considerations; 6 Conclusion; References; Chapter 2: Systematic Review and€Meta-analysis: Important Tools in€Understanding Drug Development for€Stroke; 1 Introduction; 2 Evidence-Based Approaches to€Understanding Translational Stroke Research; 2.1 Assessing the€Quality and€Range of€Available Evidence; 2.1.1 Quality of€Evidence; 2.1.2 Range of€Evidence; 2.2 Assessing for€Publication Bias; 2.3 Impacts of€Systematic Reviews.

This book is a critical and comprehensive look at current state-of-the-art scientific and translational research being conducted internationally, in both academia and industry; it serves to address new ways to provide effective treatment to victims of ischemic and hemorrhagic stroke and other ischemic diseases. Currently, stroke can be successfully treated through the administration of a thrombolytic, but the therapeutic window is short and many patients are not able to receive treatment. Only about 30% of patients are "cured" by available treatments. Divided into five sections, the proposed volume explores historical and novel neuroprotection mechanisms and targets, new and combination therapies, as well as clinical trial design for some of the most recent bench-side research.