Paul R. Sanberg – författare

Prominent experimentalists critically review the animal models widely used in developing powerful new therapies for central nervous system diseases. Coverage includes novel uses of animal models of Alzheimer's, Parkinson's, and Huntington's diseases, and studies of aging. Techniques that rely heavily on behavioral analyses, as well as models developed from infusions of neurotoxins and from advances in molecular biology, are thoroughly explicated, as are models developed for more acute neurological conditions, including traumatic brain injury and stroke. Comprehensive and authoritative, Central Nervous System Diseases: Innovative Animal Models from Lab to Clinic offers neuroscientists, pharmacologists, and interested clinicians a unique survey of the most productive animal models of the leading neurological diseases currently employed to develop today's innovative drug therapies.

Mitochondria have long been the Rodney Dangerfield of cellular organelles. Believed to be the remnants of bacterial infection of eukaryotic cells eons ago, the mitochondrion evolved a symbiotic relationship in which it dutifully served as the efficient source of A TP for cell function. The extraordinary dependence of cells on the energy provided by mito­ chondrial oxidative metabolism of glucose, especially through critical organs such as the heart and brain, is underlined by the fatal consequences of toxins that interfere with the mitochondrial electron transport system. Consistent with their ancestry, the mitochondria have their own DNA that encodes many but not all of their proteins. The mitochon­ dria and their genes come from the mother via the ovum since sperm do not possess mitochondria. This extranuclear form of inheritance derived exclusively from the female side has proven to be a powerful tool for tracing the evolution by the number of base substitutions in mtDNA. That mitochondrial gene mutations might be a source of human dis­ ease became evident a decade ago with the characterization of a group of multisystem disorders, typically involving the nervous system, which are transmitted from mother to child. Specific point mutations in mtDNA have been associated with the different syndromes.

An authoritative survey of the most recent scientific evidence showing how cyclosporin, FK-506, and their analogs-the neuroimmunophilins-evolved from being purely immunosuppressant "drugs" to neuroprotective "agents". The book focuses on recent preclinical evidence that demonstrates the neurotrophic/neuroprotective effects of immunosuppressants when administered alone or when combined with neural transplantation therapy in animal models of neurological disorders. It also discusses their efficacy and mechanisms of action in vitro and in vivo models of CNS disease, and provides laboratory studies with compelling clinical indications for Alzheimer's disease, Huntington's disease, stroke, traumatic brain injury, spinal cord injury, ALS, sciatic nerve injury, and drug addiction.

An authoritative survey of the most recent scientific evidence showing how cyclosporin, FK-506, and their analogs-the neuroimmunophilins-evolved from being purely immunosuppressant "drugs" to neuroprotective "agents". The book focuses on recent preclinical evidence that demonstrates the neurotrophic/neuroprotective effects of immunosuppressants when administered alone or when combined with neural transplantation therapy in animal models of neurological disorders. It also discusses their efficacy and mechanisms of action in vitro and in vivo models of CNS disease, and provides laboratory studies with compelling clinical indications for Alzheimer's disease, Huntington's disease, stroke, traumatic brain injury, spinal cord injury, ALS, sciatic nerve injury, and drug addiction.

Mitochondria have long been the Rodney Dangerfield of cellular organelles. Believed to be the remnants of bacterial infection of eukaryotic cells eons ago, the mitochondrion evolved a symbiotic relationship in which it dutifully served as the efficient source of A TP for cell function. The extraordinary dependence of cells on the energy provided by mito­ chondrial oxidative metabolism of glucose, especially through critical organs such as the heart and brain, is underlined by the fatal consequences of toxins that interfere with the mitochondrial electron transport system. Consistent with their ancestry, the mitochondria have their own DNA that encodes many but not all of their proteins. The mitochon­ dria and their genes come from the mother via the ovum since sperm do not possess mitochondria. This extranuclear form of inheritance derived exclusively from the female side has proven to be a powerful tool for tracing the evolution by the number of base substitutions in mtDNA. That mitochondrial gene mutations might be a source of human dis­ ease became evident a decade ago with the characterization of a group of multisystem disorders, typically involving the nervous system, which are transmitted from mother to child. Specific point mutations in mtDNA have been associated with the different syndromes.

As our world continues to evolve, the field of regenerative medicine f- lows suit. Although many modern day therapies focus on synthetic and na- ral medicinal treatments for brain repair, many of these treatments and prescriptions lack adequate results or only have the ability to slow the p- gression of neurological disease or injury. Cell therapy, however, remains the most compelling treatment for neurodegenerative diseases, disorders, and injuries, including Parkinson’s disease, Huntington’s disease, traumatic brain injury, and stroke, which is expanded upon in more detail in Chapter 1 by Snyder and colleagues. Cell therapy is also unique in that it is the only therapeutic strategy that strives to replace lost, damaged, or dysfunctional cells with healthy ones. This repair and replacement may be due to an administration of exogenous cells itself or the activation of the body’s own endogenous reparative cells by a trophic, immune, or inflammatory response to cell transplantation. However, the precise mechanism of how cell therapy works remains elusive and is c- tinuing to be investigated in terms of molecular and cellular responses, in particular. Moreover, Chapter 11 by Emerich and associates, discusses some of the possibilities of cell immunoisolation and the potential for treating central nervous system diseases.

Over the last decade, neural stem cell research has provided penetrating insights into the plasticity and regenerative potential of the brain. Stem cells have been isolated from embryonic as well as adult central nervous system (CNS). Many non-CNS mammalian tissues also contain stem cells with a more limited repertoire: the replacement of tissue-specific cells throughout the li- time of the organism. Progress has been made in understanding fundamental stem cell properties that depend on the interplay of extrinsic signaling factors with intrinsic genetic programs within critical time frames. With this growing knowledge, scientists have been able to change a neural stem cell’s fate. - der certain conditions, neural stem cells have been induced to differentiate into cells outside the expected neural lineage and conversely, stem cells from nonneural tissue have been shown to transdifferentiate into cells with distinct neural phenotypes. At the moment, there is an accelerated effort to identify a readily ava- able, socially acceptable stem cell that can be induced to proliferate in an und- ferentiated state and that can be manipulated at will to generate diverse cells types. We are on the threshold of a great new therapeutic era of cellular therapy that has as great, if not greater, potential as the current pharmacologic era, g- rified by antibiotics, anesthetics, pain killers, immunosuppressants, and psyc- tropics.

Prominent experimentalists critically review the animal models widely used in developing powerful new therapies for central nervous system diseases. Coverage includes novel uses of animal models of Alzheimer''s, Parkinson''s, and Huntington''s diseases, and studies of aging. Techniques that rely heavily on behavioral analyses, as well as models developed from infusions of neurotoxins and from advances in molecular biology, are thoroughly explicated, as are models developed for more acute neurological conditions, including traumatic brain injury and stroke. Comprehensive and authoritative, Central Nervous System Diseases: Innovative Animal Models from Lab to Clinic offers neuroscientists, pharmacologists, and interested clinicians a unique survey of the most productive animal models of the leading neurological diseases currently employed to develop today''s innovative drug therapies.

Mitochondria have long been the Rodney Dangerfield of cellular organelles. Believed to be the remnants of bacterial infection of eukaryotic cells eons ago, the mitochondrion evolved a symbiotic relationship in which it dutifully served as the efficient source of A TP for cell function. The extraordinary dependence of cells on the energy provided by mito­ chondrial oxidative metabolism of glucose, especially through critical organs such as the heart and brain, is underlined by the fatal consequences of toxins that interfere with the mitochondrial electron transport system. Consistent with their ancestry, the mitochondria have their own DNA that encodes many but not all of their proteins. The mitochon­ dria and their genes come from the mother via the ovum since sperm do not possess mitochondria. This extranuclear form of inheritance derived exclusively from the female side has proven to be a powerful tool for tracing the evolution by the number of base substitutions in mtDNA. That mitochondrial gene mutations might be a source of human dis­ ease became evident a decade ago with the characterization of a group of multisystem disorders, typically involving the nervous system, which are transmitted from mother to child. Specific point mutations in mtDNA have been associated with the different syndromes.

As our world continues to evolve, the field of regenerative medicine f- lows suit. Although many modern day therapies focus on synthetic and na- ral medicinal treatments for brain repair, many of these treatments and prescriptions lack adequate results or only have the ability to slow the p- gression of neurological disease or injury. Cell therapy, however, remains the most compelling treatment for neurodegenerative diseases, disorders, and injuries, including Parkinson’s disease, Huntington’s disease, traumatic brain injury, and stroke, which is expanded upon in more detail in Chapter 1 by Snyder and colleagues. Cell therapy is also unique in that it is the only therapeutic strategy that strives to replace lost, damaged, or dysfunctional cells with healthy ones. This repair and replacement may be due to an administration of exogenous cells itself or the activation of the body’s own endogenous reparative cells by a trophic, immune, or inflammatory response to cell transplantation. However, the precise mechanism of how cell therapy works remains elusive and is c- tinuing to be investigated in terms of molecular and cellular responses, in particular. Moreover, Chapter 11 by Emerich and associates, discusses some of the possibilities of cell immunoisolation and the potential for treating central nervous system diseases.

Prominent experimentalists critically review the animal models widely used in developing powerful new therapies for central nervous system diseases. Coverage includes novel uses of animal models of Alzheimer's, Parkinson's, and Huntington's diseases, and studies of aging. Techniques that rely heavily on behavioral analyses, as well as models developed from infusions of neurotoxins and from advances in molecular biology, are thoroughly explicated, as are models developed for more acute neurological conditions, including traumatic brain injury and stroke. Comprehensive and authoritative, Central Nervous System Diseases: Innovative Animal Models from Lab to Clinic offers neuroscientists, pharmacologists, and interested clinicians a unique survey of the most productive animal models of the leading neurological diseases currently employed to develop today's innovative drug therapies.