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Nanomedicine in Central Nervous System Injury and Repair

1st Edition - November 11, 2017

Editors: Hari Shanker Sharma, Peter Jenner, Aruna Sharma

Hardback ISBN:

9 7 8 - 0 - 1 2 - 8 1 2 3 8 1 - 2

eBook ISBN:

9 7 8 - 0 - 1 2 - 8 1 2 3 8 2 - 9

Nanomedicine in Central Nervous System Injury and Repair (IRN), Volume 137, the latest release in the International Review of Neurobiology series presents comprehensive chapters… Read more

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Nanomedicine in Central Nervous System Injury and Repair (IRN), Volume 137, the latest release in the International Review of Neurobiology series presents comprehensive chapters that cover a broad range of topics, including, but not limited to, how Diabetes exacerbates methamphetamine induced blood-brain barrier breakdown, edema formation, oxidative stress and myelin damage, and how Focal blast brain injury induces rapid edema formation, blood-brain barrier breakdown and intensive cellular damage. In addition, the Neuroprotective effects of a multimodal drug cerebrolysin are explored, as is how Nanowired cerebrolysin potentiates neuroprotective effects of histamine H3 receptor inverse agonist and antagonist with partial H4 agonist in Alzheimer's Disease.

This series reviews current knowledge and understanding on how to repair the damaged spinal cord and brain with nanomedicine, detailing new therapeutic advances and providing a starting point for researchers and practitioners entering the field.

Cover image
Title page
Table of Contents
Copyright
Contributors
Preface
Acknowledgments
Chapter One: Current Strategies for the Delivery of Therapeutic Proteins and Enzymes to Treat Brain Disorders
Abstract
1 Introduction
2 Physical Delivery
3 Nonphysical Methods
4 Conclusion
Chapter Two: Impact of Inflammation on the Blood–Neural Barrier and Blood–Nerve Interface: From Review to Therapeutic Preview
Abstract
1 Introduction
2 Blood–Nerve Interface
3 Mast Cells and the BBB
4 Immune Cell Interactions Amplify Neuroinflammation
5 Neuroinflammation and Aging
6 Mast Cells and Glia as Therapeutic Targets
7 Conclusion and Perspectives
Acknowledgments
Conflict of Interest
Chapter Three: Intravenous Administration of Functionalized Magnetic Iron Oxide Nanoparticles Does Not Induce CNS Injury in the Rat: Influence of Spinal Cord Trauma and Cerebrolysin Treatment
Abstract
1 Introduction
2 Experimental Procedures
3 SCI Model
4 Nanoparticle Administration
5 Treatment With Cerebrolysin
6 Effects of Cerebrolysin on BBB/BSCB Permeability
7 Conclusion and Future Perspectives
Acknowledgments
Chapter Four: Histaminergic Receptors Modulate Spinal Cord Injury-Induced Neuronal Nitric Oxide Synthase Upregulation and Cord Pathology: New Roles of Nanowired Drug Delivery for Neuroprotection
Abstract
1 Introduction
2 Histamine in the Spinal Cord
3 Histamine and Nitric Oxide Interaction
4 Histamine and the Spinal Cord Microcirculation
5 Histamine and the BSCB Permeability
6 Histamine and Spinal Cord Edema
7 Nanowired Drug Delivery Enhances Neuroprotection
8 Our Investigations on Histamine-Receptor Modulation and nNOS Expression in SCI
9 Histamine Receptors Influence Spinal Cord Pathology and nNOS Expression
10 Histamine-Receptor Modulation and BSCB in SCI
11 Histamine-Receptor Modulation and SCBF in SCI
12 Histamine-Receptor Modulation and Spinal Cord Edema in SCI
13 Histamine-Receptor Modulation and Neuronal NOS Expression in SCI
14 Histamine-Receptor Modulation and Neuronal Changes in SCI
15 TiO2-Nanowired Delivery of Histamine H2 Receptor Antagonists Has Superior Neuroprotective Effects in SCI
16 Functional Significance of Our Findings
Acknowledgments
Chapter Five: Nanoformulation: A Useful Therapeutic Strategy for Improving Neuroprotection and the Neurorestorative Potential in Experimental Models of Parkinson's Disease
Abstract
1 Introduction
2 Development
3 Conclusions
Acknowledgments
Chapter Six: Novel Treatment Strategies Using TiO2-Nanowired Delivery of Histaminergic Drugs and Antibodies to Tau With Cerebrolysin for Superior Neuroprotection in the Pathophysiology of Alzheimer's Disease
Abstract
1 Introduction
2 Histaminergic Mechanism
3 Histamine Actions in the Brain
4 Role of Histamine in AD
5 Histamine as a Mediator for Peripheral Immune Cells
6 Antihistaminergic Drugs
7 Antibodies as Promising Tool for Neurotherapeutic Measures
8 Historical Perspectives on the Use of Antibodies as Therapy
9 Possible Therapeutic Basis of Antibodies
10 Antibodies vs Receptor Antagonist Drugs
11 Antibodies Neutralize Effects of Endogenous Antigens
12 Nanodelivery of Drugs Induces Superior Neuroprotective Effects Than Their Parent Compound
13 Antibodies Therapy in AD
14 Our Own Investigations in AD With Histaminergic Drugs and Antibodies for Neuroprotection
15 AβP Infusion Model of AD
16 Nanowired Delivery of Drugs
17 Parameters Measured
18 BBB Permeability
19 Brain Edema Formation and Volume Swelling
20 AβP (1–40) Immunohistochemistry
21 Neuronal Damages
22 Glial Fibrillary Acidic Protein Immunohistochemistry
23 Our Observations in AD Using Histaminergic Drugs and/or Antibodies
24 Nanowired Cerebrolysin Potentiates Histamine Antibodies-Induced Neuroprotection in AD
25 p-Tau Antibodies Reduces Neurotoxicity in AβP Infusion Model of AD
26 Nanowired Cerebrolysin Potentiates p-Tau Antibodies-Induced Neuroprotection in AD
27 Functional Significance of Our Findings
Acknowledgments

Hari Shanker Sharma

Dr. Hari Shanker Sharma, Professor of Neurobiology (MRC), Docent in Neuroanatomy (UU) is currently working in Uppsala University Hospital, Department of Surgical Sciences, Division of Anesthesiology & Intensive Care Medicine, Uppsala University, Sweden. Dr Sharma obtained his Masters Degree from Bihar University with special expertise in Cell Biology in 1976 and was awarded the Gold Medal of Bihar University for securing 1st position in the 1st Class. Dr Sharma joined the group of Professor Prasanta Kumar Dey, a neurophysiologist, by training in the Department of Physiology, Institute of Medical; Sciences, Banaras Hindu University, Varanasi in 1977 to obtain his Doctor of Philosophy Degree (D.Phil.) in Neurosciences and was awarded his Ph.D. in 1982 on “Blood-Brain Barrier in Stress.” After carrying out a series of Government of India funded Research Projects on the BBB and brain dysfunction (1982–1987), Dr Sharma joined the lab of Neuropathology at Uppsala University with Professor Yngve Olsson in 1988 to investigate passage of tracer transport across the BBB caused by stress or traumatic insults to the Brain and Spinal cord at light and electron microscopy. Dr Sharma was awarded the prestigious Alexander von Humboldt Foundation Fellowship of German Government (1989–1991) to work on hyperthermia induced BBB dysfunction at the ultrastructural level in the laboratory of Professor Jorge Cervós-Navarro (a living “Legend in Neuropathology in Europe”). Dr Sharma again joined Uppsala University and established a network of collaboration on “Experimental CNS Injury Research Group” as a lead investigator with eminent collaborators in various parts of Europe, USA, and Australia (1991–). On his work on hyperthermia Dr Sharma received the prestigious Neuroanatomy award “Rönnows Research prize” of Uppsala University for “best neuroanatomical research of the year 1996” followed by the Award of the Degree of Doctor of Medical Sciences of Uppsala University in Neuroanatomy in 1999 and selected for the Best Thesis Award of the Medical faculty, “The Hwassers Prize” of 1999. On his meticulous works on the Blood Brain barrier and Brain edema (2000–2003) Dr. Sharma earned the prestigious title of “Docent in Neuroanatomy” of Medical Faculty, Uppsala University in April 2004. Currently his main research interest is Neuroprotection and Neuroregeneration, in relation to the Blood-brain barrier in stress, trauma, and drugs of abuse in health and disease. Dr. Sharma on his research on brain pathology and neuroprotection in different models received the prestigious award from The Laerdal Foundation of Acute Medicine, Stavanger, Norway, in 2005 followed by Distinguished International Scientists Collaboration Award by National Institute on Drug Abuse (NIDA), Baltimore, MD (2006–2008). His recent work on 5-HT3 receptor mediated neuroprotection in morphine withdrawal induced neurotoxicity won the coveted prize of Best Investigator Award 2008 and Best Scientific Presentation by European Federation of the International Association for Study of Pain (ISAP), and Awarded during their VI Annual Meeting in Lisbon, September 9–12, 2008. His recent research is aimed to find out the role of nanoparticles in Neurodegeneration and Neuroprotection using various treatment strategies that is supported by European Aerospace Research and Development (EOARD), London, UK and US Air Force Research Laboratory, Wright Patterson Air Force Base, Dayton, Oh, USA. On his works on Blood–brain barrier in hypertension and diabetes together with Romanian colleagues, University of Medicine and Pharmacy “Iuliu Hatieganu,” Cluj-Napoca, Romania awarded Dr. Sharma with Honorary Doctorate of Medical Sciences in 2009. Dr Sharma’s work over 30 years on the blood-brain barrier and brain edema won him the US Neurosurgeon Dr Anthony Marmarou Award (2011) by the International Brain Edema Society at their 15th Congress in Tokyo, Japan, November 2011. His works on Nanoneuroscience and development of nanomedicine to treat the CNS injuries has won accolades at various Government and International Scotties or Organization across the World. Accordingly Dr Sharma was decorated with the most prestigious ”Hind Rattan Award 2012” on the eve of Republic Day of India in January 2012 and Mahatma Gandhi Pravasi Gold Medal in October 2012 in House of Lords, London, UK. Dr Sharma was also invited to organize and chair Nanosymposium in Society for Neuroscience meetings in Chicago (2009), San Diego (2010), Washington DC (2011) and New Orleans (2012). Dr Sharma has published over 380 research papers, 75 reviews, 12 monographs, and 70 international book chapters and edited 15 book volumes.

Affiliations and expertise

Professor, Uppsala University, Sweden

Peter Jenner

Professor Peter Jenner is a specialist in preclinical aspects of neurodegenerative diseases, notably Parkinson’s disease. He has spent the major part of his career at King’s College London where he was Head of Pharmacology for 14 years before returning to his research roots and subsequently becoming Emeritus Professor of Pharmacology. Peter has expertise in drug metabolism and pharmacokinetics but neuropharmacology based on functional models of neurodegenerative diseases has formed the major focus of his work. Peter holds a BPharm, PhD and DSc degree from the University of London. He has published well over 1000 articles with more than 700 peer reviewed papers. He is a Fellow of the Royal Pharmaceutical Society, the British Pharmacological Society, the Royal Society of Medicine and of King’s College London. Peter was recently honoured with a Doctor Honoris Causa degree from Carol Davila University of Medicine and Pharmacy, Bucharest and made an Honorary Fellow of The British Pharmacological Society for his contribution to research in to movement disorders. Peter has worked closely with the pharmaceutical industry for many years and acts as an adviser and consultant to both major pharma and biotech companies. He has a wide knowledge of the drug discovery and drug development process and has been involved from molecule synthesis through to drug registration for use in man. Peter was the Founder, Director and Chief Scientific Officer of Proximagen, a biotech focussed on the treatment and cure of neurodegenerative diseases that was listed on AIMs and subsequently purchased by a US based healthcare company. He is a regular speaker at international meetings and also takes time to speak at Parkinson’s disease patient-carer groups across the UK.

Affiliations and expertise

Emeritus Professor of Pharmacology, Institute of Pharmaceutical Sciences, King’s College London, London, UK

Aruna Sharma

Aruna Sharma, MD is currently Secretary of Research at Uppsala University Hospital, Uppsala University, Sweden. She obtained her Bachelor of Science in 1971 and trained in Indian Medicine up to 1977 and engaged in medical research from 1978 to 1986 in India on hyperthermia induced brain dysfunction in the lab of Hari Sharma and Prasanta Kumar Dey under University Grants Commission and Indian Council of Medical Research Her main interest is now focused on Indian Medicinal drugs and their effects on the Central Nervous System Function, toxicology, neurorepair and neuroprotection. She is also investigating neurotoxicological profiles of many Ayurvedic traditional drugs with special reference to those containing metal oxide or metal ashes.

Affiliations and expertise

Secretary of Research, Uppsala University Hospital, Uppsala University, Sweden