C
GLOSSARY OF MAJOR TERMS


Action potential

Electrical impulses that result from the influx and efflux of ions across the plasma membrane of neurons.

Antioxidants

Natural body chemicals or drugs that reduce oxidative damage, such as that caused by free radicals.

Apoptosis

Programmed cell death, a form of cell death in which a controlled sequence of events (or program) leads to the elimination of cells, minimizing the release of harmful substances into the surrounding area. Many types of cell damage can trigger apoptosis, and it also occurs normally during the development of the nervous system and other parts of the body. Strictly speaking, the term apoptosis refers only to the structural changes that cells go through, and programmed cell death refers to the complete underlying process, but the terms are often used synonymously.

Ascending pathways

Nerve pathways that carry sensory information from the body up the spinal cord toward the brain.

Astrocytes

The largest and most numerous of the supporting, or glial, cells in the brain and spinal cord. Astrocytes (meaning “star cells,” because of their shape) contribute to the blood-brain barrier, help regulate the chemical environment around cells, respond to injury, and release regulatory and trophic substances that influence nerve cells.

Autonomic dysreflexia

A potentially life-threatening increase in blood pressure, sweating, and other autonomic reflexes in reaction to bowel impaction or some other stimulus.

Autonomic nervous system

The portion of the nervous system that governs



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Spinal Cord Injury: Progress, Promise, and Priorities C GLOSSARY OF MAJOR TERMS Action potential Electrical impulses that result from the influx and efflux of ions across the plasma membrane of neurons. Antioxidants Natural body chemicals or drugs that reduce oxidative damage, such as that caused by free radicals. Apoptosis Programmed cell death, a form of cell death in which a controlled sequence of events (or program) leads to the elimination of cells, minimizing the release of harmful substances into the surrounding area. Many types of cell damage can trigger apoptosis, and it also occurs normally during the development of the nervous system and other parts of the body. Strictly speaking, the term apoptosis refers only to the structural changes that cells go through, and programmed cell death refers to the complete underlying process, but the terms are often used synonymously. Ascending pathways Nerve pathways that carry sensory information from the body up the spinal cord toward the brain. Astrocytes The largest and most numerous of the supporting, or glial, cells in the brain and spinal cord. Astrocytes (meaning “star cells,” because of their shape) contribute to the blood-brain barrier, help regulate the chemical environment around cells, respond to injury, and release regulatory and trophic substances that influence nerve cells. Autonomic dysreflexia A potentially life-threatening increase in blood pressure, sweating, and other autonomic reflexes in reaction to bowel impaction or some other stimulus. Autonomic nervous system The portion of the nervous system that governs

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Spinal Cord Injury: Progress, Promise, and Priorities involuntary actions and innervates smooth and cardiac muscles and glandular tissues. Axon Long nerve cell fibers that arise from a neuron’s cell body and that conduct electrical impulses to the target cell. Axons contact other nerve, muscle, and gland cells at synapses and release neurotransmitters that influence those cells. Axonal transport The process by which nerve cells move substances from the cell body down the axon and from the end of the axon back to the cell body. Transport down the axon is necessary because axons cannot synthesize many substances, such as proteins, that they need. Transport back to the cell body recycles substances and also carries signals taken up by axon terminals, such as trophic factors, to the cell body, where they can affect cellular processes. Blood-brain barrier Tight junctions are formed by endothelial cells that line blood vessels and regulate the entry of circulating substances and immune cells into the brain and spinal cord. Trauma may compromise these barriers and contribute to further damage in the brain and spinal cord. These barriers also prevent the entry of some potentially therapeutic drugs. Brain-derived neurotrophic factor (BDNF) Exogenous neurotrophic factor. Cell adhesion molecules Molecules on the outside surfaces of cells that bind to other cells or to the extracellular matrix (the material surrounding cells). Cell adhesion molecules influence many important functions, such as the entry of immune cells into the damaged spinal cord and the path finding of growing axons. Central nervous system (CNS) The portion of the nervous system that consists of the brain and spinal cord. The CNS coordinates the entire nervous system and is responsible for receiving sensory information from the environment and responding using motor impulses. Central pattern generator (CPG) A complex circuit of neurons responsible for coordinated rhythmic muscle activity, such as locomotion. Clinical trials Systematic studies with human patients aimed at determining the safety and effectiveness of new or unproven therapies. Systematic testing in clinical trials has four phases. Phase I trials determine both the safety of a drug or intervention and the appropriate dosage. Phase II trials, which are performed with relatively small groups of patients, establish efficacy and evaluate reported side effects. Phase III trials, which usually require much larger numbers of patients, compare the new therapies to established therapies or a placebo, or both, and continue to monitor the participants for adverse side effects. Phase IV trials are required by the FDA for additional analysis of postmarking, long-term risks, and benefits.

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Spinal Cord Injury: Progress, Promise, and Priorities Computed tomography (CT) or computer-assisted tomography (CAT) Diagnostic imaging method in which X-ray measurements obtained from many angles are combined into a single image. CT scans help physicians evaluate bone structures and bleeding within the skull and spine. Contusion A bruising injury. Spinal cord contusions result in a cavity or hole in the center of the spinal cord. Myelinated axons typically survive around the perimeter of the spinal cord, and the dura may even remain unbroken by the injury. Corticospinal tracts The nerve fibers that carry signals from the motor control areas of the brain’s cerebral cortex to the spinal cord. Cyclic AMP (cAMP) An adenosine-based mononucleotide that mediates hormonal effects and that acts as a second messenger. Cytokines Chemical messenger molecules by which immune cells communicate with one another and with other cells. Some nerve cells also use cytokines as messenger molecules. Cytoskeleton The internal scaffolding of cells. The cytoskeleton determines the cell shape, organizes structures within cells, and helps cells and growth cones of developing axons move. Dendrites The tree-like branches from nerve cell bodies that receive and integrate signals from other nerve cells at synapses. Deoxyribonucleic acid (DNA) Basic unit of heredity. DNA consists of a double helix containing ribose sugars, nucleic acids, phosphate groups, and hydrogen bonds. Dermatome Predefined regions of the skin that are innervated by nerve fibers and tested (via a pinprick or light touch) to determine sensory response. Descending pathways Nerve pathways that go down the spinal cord and that allow the brain to control the movement of the body below the head and autonomic function. Dorsal Relating to the back or posterior of an animal. Excitotoxicity Excessive release of neurotransmitters causing damage to nerve and glial cells. Excitotoxicity probably contributes to damage following nervous system trauma and stroke and may also contribute to some neurodegenerative diseases. Glutamate, the most prevalent neurotransmitter by which nerve cells excite (activate) one another, is often involved in excitotoxicity. Extracellular matrix The material that surrounds cells. Important regulatory molecules in the extracelluar matrix promote, inhibit, or guide the growth of axons. F30 fellowship Federally supported fellowship sponsored by the National Institutes of Health and given to predoctoral students seeking combined M.D. and Ph.D. degrees. These fellowships were created to increase the number of physician-researchers in the field of mental health,

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Spinal Cord Injury: Progress, Promise, and Priorities substance abuse, and environmental sciences. The fellowships, which are limited to no more than 6 years, subsidize the cost of tuition and associated fees, stipends, and certain allowable costs. F31 fellowship Federally supported fellowship sponsored by the National Institutes of Health for predoctoral students that require a dissertation research project and training program. Fellowships are typically limited to no more than 5 years and support tuition and fees, stipends, and other costs. Specific F31 fellowships are available for ethnic and racial minorities and individuals with disabilities. Fibroblast growth factor (FGF) Exogenous neurotrophic factor. Free radicals Highly reactive chemicals that attack molecules crucial for cell function by capturing electrons and thus modifying chemical structures. Gamma-aminobutyric acid (GABA) A neurotransmitter that typically inhibits subsequent neurons from being excited. Gap junction Site of communication between adjacent cells and exchange of low-molecular-weight substances. Gene expression Term used to describe those genes that are transcribed into proteins and that are active in or influence a biological process. Glia Supporting cells of the nervous system. Glial cells in the brain and spinal cord far outnumber nerve cells. They not only provide physical support but also respond to injury, regulate the chemical composition surrounding cells, participate in the blood-brain and blood-spinal cord barriers, form the myelin insulation of nerve pathways, help guide neuronal migration during development, and exchange metabolites with neurons. They may also produce substances that help and hinder regeneration in the spinal cord. The major types of glial cells in the central nervous system are astrocytes, oligodendrocytes, and microglia. Glia-derived neurotrophic factor (GDNF) Exogenous neurotrophic factor. Glutamate A neurotransmitter that elicits subsequent neurons to fire an action potential. Gray matter The parts of the brain and spinal cord composed mainly of neuronal cell bodies and dendrites and not myelinated (white) axons. The gray matter of the spinal cord lies in a butterfly-shaped region in the center of the cord. Growth cones Specialized structures at the tips of growing axons. Growth cones detect guidance signals in their environment and “steer” growing axons. Immediate-early genes Genes that respond quickly to many types of stimuli and that control the activities of other genes. They participate in the cellular programs that control regeneration and apoptosis. Interneurons Neurons in the spinal cord that primarily communicate between neurons over short distances (compare interneurons with sensory and motor neurons, whose axons project outside the cord). Spinal

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Spinal Cord Injury: Progress, Promise, and Priorities cord interneurons help integrate sensory information and generate coordinated muscle commands. Ischemia Inadequate blood flow. The brain and spinal cord are easily damaged by ischemia because of a decreased oxygen supply. Knockouts Genetically engineered animals (usually mice) in which a particular gene has been removed from the animal’s DNA. Lipid peroxidation Breakdown of membrane lipids that eventually destroy the cell. This reaction is typically caused by free-radical formation, usually from oxygen atoms, which gives rise to a series of pathological reactions inside cells. Magnetic resonance imaging (MRI) A type of diagnostic imaging technique that relies on the interactions of magnetic fields and radio-frequency radiation with body tissues. MRI is better than computed tomography scans for viewing soft tissue. Methylprednisolone A corticosteroid, similar to a natural hormone produced by the human adrenal glands. It is used to relieve inflammation and to treat certain forms of arthritis; skin, blood, kidney, eye, thyroid, and intestinal disorders (e.g., colitis); severe allergies; and asthma. Microarray Biochemical application that allows the rapid reproducibility of gene fragments of known sequence and that can be used to assess gene expression. Microglia Small cells located throughout the central nervous system that act as phagocytes and that typically engulf and destroy particulate matter. Motor neurons Nerve cells whose axons pass from the central nervous system to a muscle to regulate the muscle’s activity. Myelin The electrically insulating coating around axons that gives white matter its whitish appearance. Myelin increases the speed and reliability of signal transmission along nerve fibers. In the central nervous system, oligodendrocytes generate myelin; in the peripheral nervous system, Schwann cells generate myelin. Myelin-associated glycoprotein (MAG) An inhibitory molecule present in myelin. The response of neurons to MAG is modulated by a cyclic AMP-dependent pathway. If cyclic AMP levels increase, protein kinase A is activated and inhibition by MAG is blocked. Necrosis A type of cell death in which cells swell and break open and release their contents. The contents can damage neighboring cells and provoke inflammation. Nerve growth factor (NGF) Exogenous neurotrophic factor. Neural prosthesis An electronic or mechanical device, or both, that connects with the nervous system and supplements or replaces functions lost by disease or injury.

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Spinal Cord Injury: Progress, Promise, and Priorities Neuron A nerve cell that is responsible for transmitting and receiving information from other cells. Most neurons comprise dendrites, a cell body, and an axon. Neurotransmitter Chemicals that are released by nerve cells at synapses and that influence the activities of other cells. Neurotransmitters may excite, inhibit, or otherwise influence the activities of cells. Neurotrophic-3 (NT-3) Exogenous neurotrophic factor. Neurotrophic factor Any of a group of neuropeptides (such as nerve growth factor) that regulate the growth, differentiation, and survival of certain neurons in the peripheral and central nervous systems. Nogo A protein that is expressed only by mature oligodendrocytes and that may be responsible for some of the inhibitory activity of myelin. Different fragments of Nogo cause growth cone collapse in a classic in vitro test of motility-inhibiting effects. Oligodendrocyte A type of glial cell in the brain and spinal cord. Oligodendrocytes wrap axons with myelin, which improves the speed and reliability of impulse conduction. These cells also produce substances that inhibit the regeneration of axons in the adult central nervous system. Oxidative damage Damage to cells caused by oxidants, or chemicals that capture electrons from other substances. The production of these substances increases during certain diseases and after a trauma or stroke and contributes to the secondary damage that follows these events. P01 grant Federally supported research program project grant that is sponsored by the National Institutes of Health and that funds as many as three separate, multidisciplinary research projects that are based on a central research theme. Funding is limited to about $1 million each year in direct costs. P30 grant Federally supported center core grant that is sponsored by the National Institutes of Health and that provides funds to develop an infrastructure that supports centralized research, facilities, and resources. Core grants provide resources to investigators to help them achieve a higher level of productivity. Awards are limited to 5 years and about $500,000 in direct costs per year. P50 grant Federally supported specialized center grant that is sponsored by the National Institutes of Health and that provides funds for multi-investigator, multidisciplinary research. The purpose of the grant is to provide a higher level of integration that might not be achieved with individual research projects. Funding is limited to about $1 million each year in direct costs. Paraplegia Paralysis of the lower half of the body with involvement of legs. Peripheral nervous system (PNS) The network of nerves outside the brain and spinal cord. Unlike nerves in the central nervous system, peripheral nerves can regrow after an injury.

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Spinal Cord Injury: Progress, Promise, and Priorities Placebo An inert substance or inactive treatment given instead of a therapy that is being evaluated in a clinical trial. Plasticity The ability of neurons to modify the physical connections, thus changing the property of a neuronal circuit. Progenitor cell Any type of cell that spawns other cells. Programmed cell death Apoptosis (see above). Proprioception The unconscious perception relating to position, posture, equilibrium, or internal condition. Proteases Enzymes that degrade proteins. Proteases are important regulators of cell function, but the inappropriate activation of proteases resulting from trauma can be harmful. Protein Any of numerous naturally occurring, extremely complex substances (such as an enzyme or antibody) that consist of amino acid residues joined by peptide bonds. They are essential constituents of all living cells that are translated from the organism’s RNA. Proteoglycans Proteins on the extracellular side of the cell membrane to which sugar moieties are attached. Quadriplegia Paralysis of all four limbs, also called tetraplegia. R01 grant Federal research project grant that supports specific health-based research for 1 to 5 years. It can be investigator initiated or submitted in response to a request for application or program announcement. R03 grant Federal grant that supports small research projects for a limited period of time and with limited resources. Grants are awarded for up to 2 years with direct costs limited to $50,000 per year. R21 grant Federally supported exploratory or developmental research grant that supports the early development of an innovative project. Grants are awarded for up to 2 years, with total direct costs not to exceed $275,000 for the length of the project. Receptors Protein molecules, usually found on the surfaces of cells, that enable cells to respond to neurotransmitters, hormones, and other messenger molecules. Receptors may act directly by opening in the cell membrane ion channels that are part of the same receptor molecule, or they may indirectly by activating second messenger systems that go on to affect various processes in the cell. The term “receptor” also refers to specialized neuronal cells that receive sensory information, such as pain receptors and light receptors in the eye. Ribonucleic acid (RNA) Carries the code for a particular protein from DNA. Messenger RNA (mRNA) is translated by specialized proteins and ribosomes to form proteins. Schwann cells Glial cells in the peripheral nervous system that are primarily responsible for wrapping nerve fibers with myelin. Second messenger system Biochemical pathway within cells that is regulated by hormones or neurotransmitters, which bind to receptors on the

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Spinal Cord Injury: Progress, Promise, and Priorities cell surface. Second messengers diffuse within the cell and alter cell behavior. They amplify signals, allow a single first messenger to control several cellular processes, and help integrate the many signals that cells receive. Spasticity A state of increased muscular tone in which abnormal stretch reflexes intensify muscle resistance to passive movements. Spinal cord segments Divisions of the spinal cord along its length. Each spinal cord segment sends a pair of motor and sensory nerves to the body. Higher segments control movement and sensation in upper parts of the body, whereas lower segments control movement and sensation in lower parts of the body. Synapse The functional connection between a nerve cell axon and target cells, which may be other nerve cells, muscle cells, or gland cells. At the synapse the axon releases a chemical neurotransmitter that diffuses across a tiny gap and binds to receptors (molecules on the surface of the target cell) that then change the target cell’s behavior. Synapses may be excitatory (which increases the probability that the target cell will be activated) or inhibitory (which reduces the probability that the target cell will be activated) or may have more complex influences (such as adjusting the sensitivity of cells to other signals). Tight junction A junction formed between adjacent cells, which prevents the passage of large molecules. Transcription Molecular process by which the genetic material deoxyribonucleic acid (DNA) is used as a template to become messenger ribonucleic acid (mRNA), which is subsequently used as a template for protein production. Translation Molecular process by which messenger ribonucleic acid (mRNA), in conjunction with ribosomes, forms proteins. Trophic factor A natural cell growth and survival molecule. Neurotrophic factors are trophic factors that affect nerve cells. Ventral Relating to the belly or front of the body. White matter Areas of the brain and spinal cord that primarily contain myelinated axons. White matter is located in the outer portion of the spinal cord and surrounds the gray matter.