Main description:

This book focuses on energy metabolism and brain functions related to Cortical Spreading Depression of Leao (CSD), an important issue in brain pathophysiology. The first part of the book offers a comprehensive overview of the history and early research on CSD, and then discusses the recent advances in the technology used to map and monitor brain mitochondrial NADH redox state and other physiological functions during CSD. The chapters explore the connection between CSD and mitochondrial function under hypoxia, Ischemia and various drugs treatment, and provide a resource to scientists researching the development of CSD during various brain pathophysiological conditions.

This book is essential to scientists and students working in the field of bioenergetics of the brain and various organs and tissues in the body. The use of this technology is also crucial and applicable in the neuroscience field.

Contents:

Preface

Front Matter- Introduction and Historical Background

Aim of the book

Leao's Cortical Spreading Depression (CSD)

Aristides Leao-life History

The Discovery of the "Spreading Depression"

Back to Brazil

Conclusion

Aristides Leao -The 4 Seminal Publications (1944-1947)

Oxygen Homeostasis in Tissues

The Discovery of Oxygen

The Discovery of the Mitochondrial Function

Monitoring of Mitochondrial Function In Vivo

Brain Energy Metabolism and Mitochondrial Function During CSD

1. Basic Principles and Technology of NADH and Multiparametric Monitoring Used in Studying Cortical Spreading Depression (CSD)

1.1 Introduction

1.2 From NADH Monitoring to Multiparametric Monitoring Systems

1.2.1 Fiber Optic Based Fluorometer/Reflectometer

1.2.2 Simultaneous Monitoring of NADH by DC-Fluorometer Reflectometer Together with Monitoring of Systemic Blood Pressure and Electro Cortical Activity (ECoG)

1.2.3 Simultaneous Monitoring of NADH together with Extracellular K+, DC Steady Potential and ECoG

1.2.4 Monitoring of Brain NADH Together with Tissue pO 2 and ECoG

1.2.5 Multiparametric Assembly for Recording of NADH, Extracellular K+, H+, DC Steady Potential and ECoG

1.2.5.1 Electrode Assembly

1.2.5.2 Correction for Local DC Biopotential

1.2.5.3 NADH Fluorescence Measurement

1.2.6 Monitoring of NADH, pO2, Extracellular K+, DC and ECoG, Outside and Inside Hyperbaric Chamber

1.2.7 Simultaneous Real Time Monitoring of Brain NADH, HbO2, ECoG, DC Potential, Extracellular K+ and Ca2+

1.2.8 Simultaneous Real Time Monitoring of Brain NADH, CBF, ECoG, DC Potential, Extracellular K+ and Ca2+

1.2.9 Simultaneous Monitoring of Brain NADH, CBF, ECoG, DC Potential, Extracellular K+, Ca+2, H+

1.2.10 Multiparametric Monitoring of Neurosurgical Patients

1.2.11 Monitoring of the Mechanism of CSD Propagation

1.2.12 Multisite Monitoring of NADH and DC Potential in Rats Under Various Conditions

1.2.13 Multisite Multiparametric Monitoring of NADH, CBF and DC Potential in Rats Under Experimental Conditions

2. Single Point and Multisite monitoring of Brain NADH Fluorescence Under CSD

2.1 Introduction

2.2 Single Point Monitoring of NADH

2.3 Two Point Monitoring of NADH

2.4 Four Points Monitoring of NADH

3. Sequence of Physiological Responses and Sequence of Events Recorded During the CSD Cycle

3.1 Introduction

3.2 Effects of CSD on Cerebral Blood Flow and Brain Oxygen Consumption

3.2.1 Introduction

3.2.2 Methods

3.2.3 Results

3.2.4 Discussion

3.3 Sequence of events recorded during the CSD cycle.

3.3.1 The Use of the MPA System

3.3.2 CSD Initiation and Contralateral Responses

3.3.3 Discussion

4. Spontaneous Development of CSD Related to Brain Pathophysiological Condition

4.1 Introduction

4.2 During Anoxia, Hypoxia and Ischemia

4.3 During Exposure to Hyperbaric Hyperoxia (HBO)

4.3.1 First Study - HBO Effects on Mitochondrial NADH and ECoG

4.3.1.1 Introduction

4.3.1.2 Methodology

4.3.1.3 Results

4.3.1.4 Discussion

4.3.2 Second Study - Protection against Oxygen Toxicity by Trimethadione (TMO)

4.3.3 Third Study - Effects of CO2 under HBO

4.3.4 Fourth Study - More Factors Affecting HBO Toxicity

4.3.4.1 Effects of Pressure Level

4.3.4.2 Effects of Age

4.3.4.3 Effects of Anti-Epileptic Drugs

4.3.5 Fifth Study - Multiparametric Monitoring of CSD Under HBO

4.3.5.1 Introduction

4.3.5.2 Methods

4.3.5.3 Results

4.3.5.4 Discussion

4.4 During Drug Induced Seizure Activity

4.5 Development of CSD During and After Traumatic Brain Injury

4.5.1 First Study - Development of the TBI Model

4.5.1.1 Introduction

4.5.1.2 Technological Aspects

4.5.1.3 Results

4.5.1.4 Discussion

4.5.2 Second Study - Level of ICP and CSD after TBI

4.5.2.1 Introduction

4.5.2.2 Methods

4.5.2.3 Results

4.5.2.4 Discussion

5. The Effects of Brain Metabolic and Other Perturbations on the Responses to Induced CSD

5.1. Effect of Oxygen Availability

5.1.1 Introduction

5.1.2 Effects of Hypoxia and Normobaric Hyperoxia

5.1.3 Responses to CSD Under Ischemia

5.1.4 Responses to CSD Under Partial Ischemia - Statistical Analysis

5.2 Effect of anesthesia on the responses to CSD

5.3 Effects of hypothermia on the responses to CSD

5.3.1 Introduction

5.3.2 Our studies

5.4 Responses to CSD in the Aging Rat

6. Effects of Pharmacological Agents on CSD

6.1 Effects of Carbon Monoxide

6.1.1 First Study - Hyperbaric Oxygenation and CO Intoxication

6.1.1.1 Introduction

6.1.1.2 Methods

6.1.1.3 Results and Discussion

6.1.2 Second Study-Multiparametric Monitoring During CO Exposure

6.1.2.1 Introduction

6.1.2.2 Methods

6.1.2.3 Results

6.1.2.4 Discussion

6.1.3 Third Study - Induced CSD Following Exposure to CO

6.1.3.1 Introduction

6.1.3.2 Methods

6.1.3.3 Results

6.1.3.4 Discussion

6.1.4 Fourth Study- Hyperbaric Oxygenation After CO Exposure in Rats

6.1.4.1 Introduction

6.1.4.2 Methods

6.1.4.3 Discussion

6.2 Nitric Oxide

6.2.1 First Study - Multiparametric Responses to CSD Under Inhibition of NO Synthesis

6.2.1.1 Introduction

6.2.1.2 Methods

6.2.1.3 Results

6.2.1.4 Discussion

6.2.2 Second Study- Brain Responses to CSD and Changes in NO Levels

6.2.2.1 Introduction

6.2.2.2 Methods

6.2.2.3 Results

6.2.2.3.1 The variation of the measured parameters in the control study

6.2.2.3.2 Results:The effect of L-NAME injection on the measured parameters

6.2.2.3.3 Results - The effect of CSD waves on the measured parameters.

6.2.2.3.4 Results - CSD Amplitudes

6.2.2.3.5 Results - CSD Wave Duration

6.2.2.3.6 Results - Recovery from CSD wave

6.2.2.4 Discussion

6.3 Alcohol Effects

6.3.1 First Study - Basic Concept of Testing Alcohol Effects on CSD

6.3.2 Second Study - The Effects of Ethanol on the Responses to CSD

6.3.2.1 Introduction

6.3.2.2 Methods

6.3.2.3 Results

6.3.2.3.1 Amplitude values

6.3.2.3.2 Wave frequency (FRQ)

6.3.2.3.3 Propagation rate - VTP (mm/min)

6.3.2.4 Discussion

6.3.2.4.1 Reflectance

6.3.2.4.2 NADH redox state

6.3.2.4.3 DC potential

7. Clinical monitoring of CSD in the Human brain

7.1 Introduction

7.2 Monitoring of NADH and Other Parameters in Patients

7.3 The Discovery of CSD in the Human Cerebral Cortex

7.3.1 Introduction

7.3.2 Methods

7.3.2.1 The development of the monitoring system

7.3.2.2 Construction of the multiprobe assembly(MPA)

7.3.2.3 Patient preparation

7.3.3 Results

7.3.4 Discussion

8. CSD and the LifenLight Score

8.1 Introduction

8.1.1 The Developed Concept

8.1.2 Brain LifenLight Score (LLS)

8.2 Methodology Used

8.2.1 The multiparametric monitoring system

8.2.2 Time Sharing Fluorometer Reflectometer (TSFR).

8.2.3 Mitochondrial NADH Redox State (NADH)

8.2.4 Microcirculatory Blood Oxygenation

8.2.5 Microcirculatory Blood Flow

8.2.6 Animal Preparation

8.2.7 Real Time Data Acquisition

8.2.8 LifenLight Score (LLS)

8.3 Results

8.4 Discussion

9. Discussion and Conclusions

9.1 Introduction

9.2 The Discovery of CSD in the Human Cerebral Cortex

9.3 NADH Responses to CSD In Vivo vs. Isolated Mitochondria In Vitro.

9.4 Cortical Spreading Depression (CSD) Under Pathophysiological Conditions

9.5 Modeling brain energy metabolism and function

9.5.1 Introduction

9.5.2 The Mathematical Model

9.5.3 Results

9.5.4 Model Discussion

9.6 Future Perspectives

Back Matter- Appendix