Ischemic Injury: A Molecular Insight

 

The World Stroke Organization reports that “stroke has already reached epidemic proportions. Globally1 in 4 adults over the age of 25 will have a stroke in their lifetime. 12.2 million people worldwide will have their first stroke this year, and 6.5 million will die as a result.” Ischemic strokes are the most common type of stroke, with about 87% of all strokes being ischemic strokes. This new volume addresses this epidemic by presenting detailed studies on ischemic injury, with emphasis on the molecular-level mechanisms and the role of signaling pathways in the body, their structure, and their mechanism of action. The book focuses on molecular pharmacology plans and explains the new areas of research on the discovery of therapeutic molecules that can be used for combating this life-threatening disease. The authors discuss stroke occurrence at different stages of life as well as sex-based differences in its treatment. They cover aspects of the clinical treatment and diagnosis of patients with cardiovascular events, including in-depth information on the prevention, evaluation, therapy selection, result projection, and long-term course of the disease in affected patients. They also detail the involvement of platelets, neurotransmitters, renin-angiotensin-aldosterone system, and vitamin D in ischemic injury.

 

Table of Contents:

 

Chapter 1 Stroke Insight

1.1 Introduction

1.1.1 Classification

1.1.2 Diagnosis

1.2 Pathophysiology

1.3 Prevention

1.3.1 Secondary Prevention

1.4 Therapy

1.5 Supportive Care

1.6 Conclusion

References

Chapter 2 Myocardial Ischemic-Reperfusion Injury

2.1 Introduction

2.2 Mechanisms and Mediators in Myocardial Ischemia/Reperfusion Injury

2.3 Factors Leading to Worsening of Myocardial Ischemia

2.4 Cardioprotective Strategies

2.4.1 Ischemic Conditioning

2.4.2 Ischemic Postconditioning

2.4.3 Remote Ischemic Conditioning

2.4.4 Pharmacological Cardioprotection

2.4.5 Hypothermia

2.5 Complications Associated with Myocardial Ischemiareperfusion Injury

2.6 Mechanistic Overview

2.7 Conclusion and Future Directions

References

Chapter 3 Preclinical and Clinical Aspects of I/R Injuries

3.1 Introduction

3.2 Ischemic/Reperfusion Injury (I/R Injury) Pathologies

3.2.1 Oxidative Stress and Inflammation: Major Pathologies of I/R Injuries

3.2.2 I/R-Induced Apoptosis

3.2.3 Role of Mitochondrial Nadph Oxidase System in Ir Injuries

3.3 Pathologies of CNS I/R Injuries

3.3.1 Pathological Events During CNS/IR Injuries

3.4 Cvs I/R Injury Pathologies

3.5 Available Treatments For I/R Injury

3.5.1 Non-Pharmacological Strategies for I/R Injuries

3.5.2 Pharmacological Approaches for I/R Injuries

3.6 Recent Data Available on Preclinical and Clinical Reports on I/R Injuries

3.7 Conclusion

References

Chapter 4 Molecular Aspects of Ischemic Reperfusion Injury

4.1 Introduction

4.2 Mechanistic Concepts of Ischemic Reperfusion Injury

4.3 Oxidative Stress System Involved in Ischemic Reperfusion Injury

4.3.1 Nadph Oxidase System

4.3.2 Xanthine Oxidase System

4.3.3 Mitochondrial Electron Transport Chain

4.4 Cell Death Mechanism Involved in Ischemic Reperfusion Injury

4.41 Autophagy

4.42 Apoptosis/Mitoptosis

4.43 Necrosis/Necroptosis

4.5 Conclusion

References

Chapter 5 Role of Mitochondria in Ischemic-Reperfusion Injury

5.1 Introduction

5.1.1 Mechanism of Ischemia-Reperfusion Injury

5.1.2 Mitochondria

5.2 Electron Transport Chain Damage and Its Molecular Pathology

5.2.1 Complex I

5.2.2 Complex Ii

5.2.3 Complex Iii

5.2.4 Complex IV–Cardiolipin

5.2.5 Cytochrome C

5.3 Ros

5.4 Reactive Nitrogen Species

5.5 Disturbances of Ions

5.6 Ischemic Reperfusion Injury and Mitochondrial Fission

5.7 The Mitochondrial Permeability Transition

5.8 mPTP and Mitophagy

5.8.1 Pathological Implications of mPTP Opening

5.9 Cell Damage in Ischemia-Reperfusion Injury

5.9.1 Mitoptosis and Apoptosis

5.9.2 Necroptosis and Necrosis

5.9.3 Autophagy

5.1.0 Conclusion

References

Chapter 6 Stroke and its Effects in Daily Life

6.1 Introduction

6.2 National And International Status Of Stroke

6.3 How Does Stroke Affect in Everyday Life?

6.3.1 Fatigue Effect

6.3.2 Effect of Acupuncture

6.3.3 Visual Loss

6.3.4 Effects Of Gardening

6.3.5 Incontinence

6.3.6 Shoulder Pain

6.4 Risk Factors

6.4.1 Smoking

6.4.2 Diabetes Mellitus

6.4.3 Alcoholism

6.4.4 Cholesterol

6.4.5 Hypertension

6.4.6 Drug Abuse

6.5 Preventive Measures And Biomarkers

6.5.1 Telestroke Capacity

6.5.2 Antiplatelet Therapy (Table 6.1)

6.5.3 Mechanical Thrombectomy

6.5.4 Anticoagulants

6.5.5 Surgical Therapies

6.6 Herbal Drugs to Treat Stroke

6.6.1 Aqueous Extract Of Saffron

6.6.2 Tetramethylpyrazine

6.6.3 Ginsenoside

6.6.4 Tanshinone

6.6.5 Gastrodin

6.6.6 Baicalin

6.6.7 Ginkgo Biloba

6.6.8 Sanhua Decoction

6.7 Biomarkers For Stroke

6.8 Current Therapeutic Approach

6.8.1 Recanalization Treatment

6.8.2 Thrombolytics

6.8.3 Neuroprotective Agents

6.8.4 Photothermal Therapy (Ptt)

6.8.5 Nanomedicines For Ischemic Stroke

6.8.6 Peptides

6.9 Future Directions

6.9.1 Nanomedicines

6.9.2 Advancement Of Neuronal Imaging Techniques

6.9.3 Neurosteroid Treatment

6.9.4 Stem Cell Therapy

6.10 Complications (Table 6.6)

6.11 Conclusion

References

Chapter 7 Etiopathogenesis and Molecular Targets in Cerebral Ischemia: Current Understanding of Stroke and Therapeutic Approaches

7.1 Introduction

7.2 Epidemiology

7.3 Cerebral Blood Supply And Sites Of Artery Occlusion In Ischemia

7.4 Types Of Cerebral Ischemia And Clinical Manifestations

7.5 Risk Factors Of Cbf Deregulation And Is

7.6 Pathophysiologic Mechanisms

7.6.1 Glutamate-Dependent Excitatory Mechanisms

7.6.2 Glutamate-Independent Calcium Toxicity

7.6.3 Mitochondrial Dysfunction And Energy Depletion

7.6.4 Inflammation

7.6.5 Oxidative Stress

7.6.6 Ischemic Tolerance

7.7 Summary And Future Directions

References

Chapter 8 Expatiating the Pivotal Role of Matrix Metalloproteinases and Blood-Brain Barrier Disruption in Ischemic Stroke: Molecular Insights and Therapeutic Targets

8.1 Introduction

8.2 Blood-Brain Barrier Disruption And Ischemic Stroke Cross Talk

8.3 Unfolding Matrix Metalloproteinases In Ischemic Stroke

8.4 Deteriorative Role Of Mmp In Stroke

8.5 Mmps And Stroke: Footprints Of Oxidative Stress

8.6 MMPS and TPA–The Culprit Party

8.7 Neuroprotective Effects Of Matrix Metalloproteinases

8.8 Matrix Metalloproteins As A Therapeutic Target In Ischemic Stroke

8.9 Conclusions And Future Prospects

References

Chapter 9 Acute Ischemic Stroke in COVID-19 Patients

9.1 Introduction

9.2 Coronavirus And Sars-Cov-2

9.3 Pathogenesis Of Ischemic Stroke And Covid-19

9.3.1 Coagulopathy

9.3.2 Endothelial Dysfunction

9.3.3 Cardio Embolism

9.3.4 Direct Viral Invasion Of The Central Nervous System

9.3.5 Neuroimaging Features

9.4 Mechanisms Of Stroke In Covid-19

9.5 Risk Of Stroke And Covid-19 Patients

9.6 Clinical Presentation

9.7 Treatment Of Acute Ischemic Stroke (Ais) In Covid-19

9.7.1 Thromboprophylaxis

9.7.2 Intravenous Thrombolysis

9.7.3 Anesthesia For Mechanical Thrombectomy

9.7.4 Immunoglobulin Therapy

9.8 Challenges Of Managing Stroke In The Setting Of Covid-19

9.9 Conclusion And Recommendation For Future Research

References

Chapter 10 Neurotransmission Imbalance: A Major Factor in the Worsening of Ischemic Injury

10.1 Introduction

10.2 Epidemiology

10.3 Types Of Strokes

10.3.1 Hemorrhagic Shock

10.3.2 Brainstem Hemorrhage Stroke

10.4 Risk Factors

10.4.1 Smoking

10.4.2 Alcohol Consumption

10.4.3 Motor Vehicle Accidents (Mva)

10.4.4 Violence

10.4.5 Explosive Blasts

10.4.6 Firearms

10.4.7 Gender

10.4.8 Hypoxia

10.4.9 Anoxia

10.5 Neurotransmission: The Game-Changer In All Aspects

10.6 Glutamate: Hallmark Of Ischemic Injury

10.6.1 Role Of Glu Receptors

10.7 Gaba: Key In The Pathogenesis Of Ischemic Injury

10.8 Acetylcholine (Ach)

10.9 Role Of Monoamines

10.10 Conclusion

References

Chapter 11 Role of the Renin-Angiotensin-Aldosterone System (RAAS) in Amelioration of Stroke Pathophysiology

11.1 Introduction

11.2 Raas and Ischemic Reperfusion Injury

11.3 Cerebrovascular System And Stroke

11.3.1 Cerebral Inflammation Following Stroke

11.3.2 Role Of Brain Ras

11.3.3 Role Of At1 Receptors

11.3.4 Role of At2 Receptors

11.4 Cardiovascular Disorders And Ir Injury

11.4.1 Role Of Heart Ras

11.5 Modulation Of Raas

11.5.1 Ace Inhibitors In The Management Of Stroke

11.5.2 Role Of Arbs

11.6 Conclusion

References

Chapter 12 Stroke and Diabetes in Vitamin D Deficiency: Prospects of Intertwined Pathobiologies

12.1 Introduction

12.2 Correlation Between Vitamin D Deficiency And Stroke

12.2.1 Plausible Mechanisms

12.3 Hyperglycemia And Vitamin D Deficit: The New Interwoven Relationship

12.4 Molecular Mechanisms

12.4.1 Vit D Maintains the Functioning of Pancreatic Beta Cells

12.4.2 Vitamin D in Relation to Insulin Signaling and Its Sensitivity

12.5 Conclusion

References

Chapter 13 Remote Ischemic Postconditioning: An Overview

13.1 Introduction

13.2 Signal Transduction

13.2.1 Remote Stimulus

13.2.2 Automatic Axon Incentive

13.2.3 Local Synthetic/Pharmacological Incentive

13.3 Remote Ischemic Conditioning

13.3.1 Remote Ischemic Preconditioning

13.3.2 Remote Ischemic Preconditioning

13.3.3 Remote Ischemic Postconditioning

13.4 Signal Transfer

13.4.1 Neuronal Pathway

13.4.2 Humoral Pathway

13.4.3 Immune-Inflammatory Pathway

13.5 Ric Targets

13.5.1 Kidney

13.5.2 Small Intestine

13.5.3 Liver

13.5.4 Brain

13.5.5 Limb

13.5.6 Heart

13.5.7 Lung

13.5.8 Gastrointestinal Tract

13.5.9 Flap of Skeletal Muscle and Skin

13.6 Specific Mediators in Remote Ischemic Conditioning

13.6.1 Adenosine

13.6.2 Thrombocyte-Dependent Signaling

13.6.3 Erythropoietin

13.6.4 Ribonucleic Acid

13.6.5 Apolipoprotein A-I

13.6.6 Biomolecules

13.6.7 Gcg-Related Peptide 1

13.6.8 Stromal Unit Originated Factor-1Α

13.6.9 Lymphocyte Activating Factor Alpha

13.6.10 Interleukin-10

References

Chapter 14 Sex-Based Differences in Acute Kidney Injury: Lessons from Renal Ischemia-Reperfusion Injury Model in Rodents

14.1 Introduction

14.2 Ischemia Reperfusion-Induced Aki

14.3 Sex Difference and Aki

14.4 Mechanisms of Estrogen-Mediated Renoprotection

14.5 Role of Ppar-Γ in Kidney Disease

14.6 Estradiol Ameliorates I/R-Induced Aki Through Ppar-γ Agonism

14.7 Role of No in Kidneys

14.8 Sex Difference and No in Renal Pathophysiology

14.9 Nmda and Kidney

14.10 Estrogen, Nmdar, and Kidney Injury

14.11 Conclusion

References

Chapter 15 Critical Overview of Conditioning Techniques and Their Current Status in the Treatment of Myocardial Ischemia-Reperfusion Injury

15.1 Introduction

15.2 Myocardial Ischemia-Reperfusion (Ir) Injury

15.2.1 Pathological Mechanism Of Myocardial Ischemia snd Ir Injury

15.3 Ischemic Preconditioning (Ipc)

15.3.1 Phases of Cardio Protection Activated by Ipc

15.3.2 Various Cardioprotective Signaling Pathways (Mechanisms) Activated/Deactivated By Ipc

15.3.3 Clinical Applications of Ipc in Cardiovascular Disorders

15.3.4 Disadvantages of IPC

15.4 Remote Ischemic Preconditioning (RIPC)

15.4.1 Cardioprotective Signaling Mechanisms Underlying RIPC

15.4.2 Clinical Applications of RIPC in Various Cardiovascular Disorders

15.5 Ischemic Postconditioning (IPostC)

15.5.1 Cardioprotective Signaling Pathways Underlying IPostC

15.5.2 Clinical Applications of IPostC in Various Cardiovascular Disorders

15.6 Remote Ischemic Postconditioning (Ripostc)

15.6.1 Cardioprotective Signaling Mechanisms Underlying Ripostc

15.6.2 Clinical Applications of Ripostc in Cardiovascular Disorders

15.7 Various Challenges Facing Clinical Research

15.8 Conclusion and Future Directions

Acknowledgments

Conflict of Interest

Authors Contribution

References

Chapter 16 Involvement of Platelets in Myocardial Ischemia and Reperfusion Injury

16.1 Introduction

16.2 Cardioprotective Effect of Platelets

16.2.1 Platelets with a Direct Cardioprotective Effect

16.2.2 Platelets with an Indirect Cardioprotective Effect

16.3 Antiplatelet Therapy's Cardioprotective Effects

16.4 Conclusion

References

Chapter 17 Recent Advancements in Strategies for the Treatment of Cerebral Ischemia

17.1 Introduction

17.2 Epidemiology

17.2.1 Age-Specific Stroke

17.2.2 Gender-Specific Stroke

17.2.3 Geographic Variation

17.2.4 Socioeconomic Variation

17.3 Pathophysiology of Stroke

17.4 Risk Factors

17.5 Targeted Drugs for Ischemic Stroke

17.6 Neuroprotective Agents

17.7 Thrombolytic Agents

17.8 Pre-Clinical Studies

17.9 Clinical Studies

17.10 Conclusions

References

Chapter 18 Recent Therapeutic Approaches Toward the Management of Ischemic Heart Disease

18.1 Introduction

18.2 Disease Pathophysiology

18.3 Various Treatments In Ischemic Heart Disease

18.4 List Of Approved Drugs Used In Ischemic Heart Disease

18.4.1 Organic Nanoparticles

18.4.2 Inorganic Nanoparticles

18.5 Conclusion

References

Chapter 19 Nanotechnology-Assisted Treatment for Ischemic Heart Disease and Related Recent Patents

19.1 Introduction

19.2 Disease Pathophysiology

19.3 Risk Parameters for IHD

19.4 Impact Of Nanotechnology On Ischemic Heart Disease

19.5 Organic Nanoparticles

19.6 List of Clinical Trials/Recent Patents

19.7 Conclusion

References

Chapter 20 Major Risk Factors Involved in the Pathobiology of Ischemic Brain and Heart Disorders

20.1 Introduction

20.2 Global Epidemiology Of Stroke

20.3 Types Of Risk Factors For Stroke

20.3.1 Modifiable

20.3.2 Non-Modifiable

20.4 Conclusion

References

Chapter 21 Modulating Mitogen-Activated Protein Kinase (MAPK) Downstream Signaling Pathways in Cerebral Ischemic Hemorrhages

21.1 Introduction

21.2 Mapk Pathway

21.2.1 The Erk1/2 Mapk Pathway

21.2.2 The P38 Mapk Pathway

21.2.3 The Jnk Mapk Pathway

21.2.4 The Erk5 Mapk Pathway

21.2.5 The Mapk Signaling Pathway And Stroke

21.3 Effect Of Mapk In Cerebral Ischemia

21.4 Effect Of Mapk In Intracerebral Hemorrhage

21.5 Effect of Mapk in Subarachnoid Hemorrhage

21.6 Conclusion

References

Chapter 22 Implication of Mitogen-Activated Protein Kinase (MAPK) in Cerebral Stroke

22.1 Introduction

22.2 Mapk Signaling And Its Subtypes

22.2.1 Apoptosis Signal-Regulating Kinase 1 (Ask1)

22.2.2 Extracellular Signal Regulated Kinase ½ (ERK1/2) Signaling

22.3 Mapk Signaling in Stroke: Protective or Aggressive/A Doubleedged Sword

22.3.1 Protective Mapk Molecular Signaling

22.3.2 Aggressive Mapk Signaling In Stroke

22.4 After Ischemic Stroke Signaling Through P38 Mapk Signaling

22.4.1 Astrocyte Activation

22.4.2 Glial Scar Formation

22.5 Cell Apoptosis and Mapk Signaling

22.6 miRNA Targeting Stroke Via Mapk Signaling

22.7 Jnk Mapk Pathway

22.8 Approaches to Obstruct Mapk in Stroke

22.9 Conclusion

References

Chapter 23 Regulation of JNK Signaling Pathway in Ischemia/Reperfusion Injury

23.1 Introduction

23.2 JNK Signaling Pathway

23.3 Pathophysiological Role of the JNK Pathway in Stroke

23.4 Targeting The JNK Pathway as a Therapeutic Protective Strategy For Different Ischemic Injury

23.4.1 JNK Signaling Pathway and Cerebral Ischemic-Reperfusion Injury

23.4.2 Jnk Signaling Pathway And Myocardial Ischemic-Reperfusion Injury

23.4.3 JNK Signaling Pathway and Renal Ischemic-Reperfusion Injury

23.4.4 JNK Signaling Pathway and Hepatic Ischemic-Reperfusion Injury

23.4.5 Jnk Signaling Pathway And Intestine Ischemic-Reperfusion Injury

23.5 Conclusion

23.6 Future Perspectives

References

Chapter 24 Role of Glycogen Synthase Kinase-3β (Gsk-3β) in Intracranial Hemorrhage

24.1 Introduction

24.2 Introduction To Glycogen Synthase Kinase-3 (GSK-3Β)

24.3 Structure and Subunits of GSK-3Β

24.4 Regulation Of GSK3-Β Activity

24.5 Role Of GSK3-Β in Cerebral Ischemic Stroke

24.6 Role of GSK3 Β in Brain Hemorrhage

24.7 Role of Gsk3Β in Subarachnoid Hemorrhage

24.8 Conclusion

References

Chapter 25 Role of GSK-3 Inhibition in Modulating the Pathology of Stroke

25.1 Introduction

25.2 Mechanistic Approaches Contributing to Stroke

25.2.1 Cell Death Mechanism

25.2.2 Inflammation

25.3 Stroke and Gsk

25.4 Signaling Involved GSK and Stroke

25.4.1 Wnt/β-Catenin Signaling

25.4.2 Pi3k/Akt/Gsk Signaling

25.4.3 NF-κB Signaling

25.4.4 Mapk

25.4.5 Tak1 and Gsk Signaling

25.4.6 Drp-1 and GSK

25.4.7 Nrf2 and GSK

25.5 Therapies to Overcome a Stroke

25.6 Conclusion

References

Chapter 26 Regulation of Nrf-2 Signaling Pathway in Ischemia/Reperfusion Injury

26.1 Introduction

26.2 Structure of NRF2

26.3 Nrf2-Are Pathway

26.4 Nrf2 Functions and Its Target Genes

26.4.1 Xenobiotics Detoxification

26.4.2 Antioxidant

26.4.3 Anti-Inflammation

26.5 Role of Nrf2 in Different Types of Ischemic Injury

26.5.1 Role Of Nrf2 in Cerebral Ischemia

26.5.2 Role of Nrf2 in Renal I/R Injury

26.5.3 Role of Nrf2 in Intestinal I/R Injury

26.5.4 Role of Nrf2 in Hepatic I/R Injury

26.5.5 Role Of Nrf2 In Cardiac I/R Injury

26.6 Conclusion

References

Chapter 27 Regulation of PI3K-Akt Signaling Pathway in Ischemia/Reperfusion Injury

27.1 Introduction

27.2 Pi3k-Akt Pathway

27.2.1 Pathophysiological Role of Pi3k Pathway in Ischemic Injury

27.3 Pi3k-Akt Signaling Pathways And Different Types Of I/R Injury

27.3.1 Pi3k-Akt Signaling And Myocardial I/R Injury

27.3.2 Pi3k-Akt Signaling And Renal I/R Injury

27.3.3 Pi3k-Akt Signaling And Cerebral I/R Injury

27.3.4 Pi3k-Akt Signaling and Hepatic I/R Injury

27.4 Conclusion

27.5 Future Perspective

References

Chapter 28 COVID-19 and Ischemic Stroke: Advancements and Challenges

28.1 Stroke And Covid-19

28.2 Sars-Cov-2: Signaling System And Immune Response

28.3 Etiology Of Covid-19 Influenced Stroke

28.4 Mechanisms Of Sars-Cov-2 Associated Stroke

28.4.1 Renin-Angiotensin System (Ras) Imbalance

28.4.2 Endothelial Dysfunction

28.4.3 Thromboinflammation

28.4.4 Cytokine Storm In Covid-19

28.4.5 Tissue Factor Coagulation Pathway

28.4.6 Complement Pathway Activation

28.4.7 Immune-Response Mediated Coagulopathy And Thrombosis

28.4.8 Damage To The Neurovascular System By Sars-Cov-2 Virus

28.4.9 Role Of Cardiac Embolism And Cardiopathy In Covid-19-Related Stroke

28.5 Clinical Presentation

28.6 Diagnosis And Management Of Covid-Associated Stroke

28.6.1 Management of Ischemic Stroke in Covid-19

28.7 Future Perspectives And Concluding Remarks

References

Index

 

An aparitie	2024
Autor	Thakur Gurjeet Singh, Heena Khan
Dimensiuni	178 x 254 mm
Editura	CRC Press
Format	Hardcover
ISBN	9781774915400
Limba	Engleza
Nr pag	564