Cellular, Molecular, Physiological, and Behavioral Aspects of Spinal Cord Injury

Description

Spinal injury affects about 10 million people annually worldwide, impacting on the family unit and causing lifelong disabilities, with varied symptoms including paresthesia, spasticity, loss of motor control, and often severe pain. Cellular, Molecular, Physiological, and Behavioral Aspects of Spinal Cord Injurywill enhance readers’ understanding of the biological and psychological effects of spinal cord injury. Featuring chapters on gene expression, metabolic effects, and behavior, this volume discusses in detail the impact of spinal cord injury to better understand the underlying pathways and processes. The book has applicability for neuroscientists, neurologists, clinicians, and anyone working to better understand these injuries. Front Cover Cellular, Molecular, Physiological, and Behavioral Aspects of Spinal Cord Injury: The Neuroscience of Spinal Cord Injury Copyright Dedication Contents Contributors Preface Section A: Setting the scene and introductory chapters Chapter 1: Causes of spinal injury: Motor vehicle accidents and beyond Introduction Spinal injury in automobile drivers Role of seatbelt and airbag in protecting spine Prevention of spinal injury among motorcycle riders Application to other areas of neuroscience Mini-dictionary of terms Key facts of spinal injury simulation Summary points References Chapter 2: Magnetic resonance imaging (MRI) findings in spinal cord injury during acute and chronic phases Introduction MRI sequences used in SCI Conventional MRI Novel and quantitative MRI sequences Protocols for MRI in SCI MRI findings in acute SCI Extra-medullary findings Ligamentous injury Disc damage Other soft tissues Vascular injury Extramedullary hematoma Fractures Intramedullary findings Cord concussion Cord compression Cord edema Hemorrhagic contusion Cord hematoma Cord ischemia Cord transection MRI findings in subacute SCI Subacute progressive ascending myelopathy Early syrinx MRI findings in chronic SCI Neurodegeneration and demyelination of the spinal cord post SCI Neurodegeneration of the brain post-SCI Conclusion Applications to other areas of neuroscience Mini-dictionary of terms Key facts of SPAM Summary points References Chapter 3: Exercise programs and spinal cord injury (SCI): Linking the clinical, physiological, and psychological consequ ... Prevalence and consequences of spinal cord injury Clinical, physiological, and psychological consequences of SCI (Fig. 1) Primary consequences of SCI: Paralysis and ANS Secondary consequences of SCI Physical inactivity and sedentary behavior Body composition and poor metabolic profile Poor musculoskeletal conditions Poor mental health and low QoL Exercise and SCI (Fig. 2) Exercise programs for people with SCI UB aerobic and strength exercise FES-assisted LB and/or WB exercise Tailored exercise for people with SCI Conclusion and future perspective Applications to other areas of neuroscience Mini-dictionary of terms Key facts on exercises and people with SCI Summary points References Chapter 4: Use of anodal transcranial direct current stimulation: Features, facets, and applications to incomplete spinal ... Introduction Discovery of the direct current therapeutic effect and technological progress Neurophysiological basis of the a-tDCS Importance of the a-tDCS after iSCI A-tDCS outcomes after iSCI CE and neuroplasticity-related outcomes Motor function and functionality outcomes Chronic neuropathic pain (NP) Other a-tDCS outcomes Characteristics of the iSCI individuals under a-tDCS protocols Parameters of the a-tDCS after iSCI Short and long-term effects of the a-tDCS A-tDCS safety and adverse effects (AEs) Clinical practice based on the a-tDCS Applications to other areas of neuroscience Dictionary of terms Key facts of anodal transcranial direct current stimulation Summary points References Further reading Chapter 5: Neuromodulation and restoration of motor responses after severe spinal cord injury Neuromodulation exploits intrinsic information processing A residual functional potential remains after SCI Central nervous system reorganization after SCI Mechanisms of spinal neuromodulation The ideal candidate for the restoration of volitional motor responses through neuromodulation Neuromuscular electrical stimulation for the recovery of independent stepping Rationale for combining NMES with other neuromodulation modalities Regaining of motor function after severe spinal cord injury Multimodal rehabilitation Applications to other areas of neuroscience Mini-dictionary of terms Key facts of neuromodulation and restoration of motor responses after severe spinal cord injury Summary points References Further reading Chapter 6: Rehabilitation and wheelchair users after spinal cord injury: An overview Introduction Epidemiology Classification and prognosis Objectives in spinal cord rehabilitation Robotic rehabilitation of movement Main clinical aspects for rehabilitation Pain Spasticity Heterotopic ossification Autonomic dysreflexia Neurogenic bladder Neurogenic bowel dysfunction Pressure ulcers Applications to other areas of neuroscience Mini-dictionary of terms Key facts of clinical classification of SCI and mobility Key facts on clinical complications of SCI Summary points References Section B: Cellular and molecular aspects of spinal injury Chapter 7: Gene expression and bone loss following spinal cord injury Introduction Incidence and pathophysiological mechanisms of spinal cord injury Altered gene expression due to spinal cord injury Bone remodeling and osteometabolic dysfunction due to SCI Molecular mechanisms of SCI-induced bone loss Acute and chronic stages of bone loss following SCI Changes in bone quality and quantity following SCI Secondary complication due to SCI-induced bone loss Conclusions Applications to other areas of neuroscience Mini-dictionary of terms Key facts of gene expression, bone loss, and spinal cord injury Summary points References Chapter 8: Sperm DNA fragmentation and its relevance to men with spinal cord injury Introduction How does SDF in men with SCI compare to other causes of infertility? Molecular mechanisms of SDF Etiologies of SDF in men with SCI Hormone alterations Elevated scrotal temperature Ejaculation frequency Sperm chromatin maturity Reactive oxygen species Leukocytospermia and ROS-related damage Sperm concentration Seminal vesicular secretions Immune function and cytokine production Other seminal plasma biochemical compounds Improving sperm DNA quality in men with SCI Conclusion Applications to other areas of neuroscience Mini-dictionary of terms Key facts of sperm DNA fragmentation Summary points References Chapter 9: Beneficial and detrimental effects of cytokines after spinal cord injury Introduction Cytokine expression after SCI Cytokines promoting cell death and neurodegeneration after SCI Cytokines in inflammation and glial scar formation Macrophage and microglia polarization Glial scar formation Cytokines in neuroprotection and repair Enhancement of antiinflammatory cytokine levels Inhibition of proinflammatory cytokine pathways Epigenetic regulation of cytokine expression Histone acetylation Noncoding RNAs Applications to other areas of neuroscience Mini-dictionary of terms Key facts Key facts of glial scar Key facts of inflammation after SCI Key facts on the major effects of cytokines Summary points References Chapter 10: Neurovascular pathology following traumatic spinal cord injury Introduction Secondary pathogenesis Hemodynamic response Neurovascular unit (NVU) Endothelial cell (EC) response Pericytic response Astrocytic response Level-specific differences in the vascular architecture of the spinal cord Therapeutic approach Pharmacological interventions Acute infusion of mesenchymal stromal cells to attenuate vascular disruption Acute IgG infusion for immunomodulation and rescue of BSCB disruption Conclusions Application to other areas of neuroscience Mini-dictionary of terms Key facts Key facts of the American Spinal Injury Association (ASIA) Impairment Scale Key facts of the spinal neurovascular unit (NVU) Summary points References Chapter 11: Protein degradome in spinal cord injury Introduction Protease-substrate repertoires Degradomes in SCI Cytoskeletal proteins Extracellular matrix Cell junction proteins Ion channels Clinical perspectives Application to other neuroscience areas Mini-dictionary of terms Key facts of spinal cord degradomics Summary points References Chapter 12: Proteomics of pressure ulcers in spinal cord injury Background Patients management Clinical proteomics Proteomics in pressure ulcers The importance of precision medicine Limitations of proteomics Conclusions Application to other areas of neuroscience Key facts of proteomics in PUs of spinal cord patients Mini-dictionary of terms Summary points References Chapter 13: Innate immune responses of glia and inflammatory cells in spinal cord injury Introduction Overview of PRRs TLRs NLRs, inflammasome complexes, and TLR-inflammasome cooperation CLRs and RLRs Role of TLRs in SCI TLR2 in SCI TLR4 in SCI TLR9 in SCI Non-immune functions of TLRs in neurons: Relevance to SCI Modulation of ECM proteins by TLRs: Relevance to SCI Applications to other areas of neuroscience Conclusions Mini-dictionary of terms Key facts of innate immunity in central nervous system injury Summary points References Chapter 14: The role of oxidative stress in spinal cord injury animal models: A focus on nuclear factor erythroid-2 relat ... Introduction Oxidative stress characteristics and mechanisms The implications of oxidative damage in SCI pathophysiology Protection mechanisms by endogenous antioxidants via Nrf2-ARE system Involvement of Nrf2 in blockage of oxidative stress post-SCI induced by exogenous stimuli Concluding remarks Application to others areas of neuroscience Mini-dictionary of terms Key facts of oxidative stress Summary points References Chapter 15: Novel agent ONO-2506 suppresses astrocytic activation and attenuates post-spinal cord injury pain Introduction Secondary injury of the spinal cord and astrocytic activation Primary and secondary injury of the spinal cord Astrocytes and their activation Reactive astrocytes and glial scarring Astrocytic activation and post-SCI neuropathic pain Mechanisms of post-SCI neuropathic pain by astrocytic activation Increase in extracellular glutamate Decrease in extracellular GABA Attenuation of post-SCI neuropathic pain by ONO-2506 S100B ONO-2506 Action mechanisms of ONO-2506 Effects of ONO-2506 on post-SCI neuropathic pain Applications to other areas of neuroscience Mini-dictionary of terms Key facts of ONO-2506 Summary points References Chapter 16: Neural tissue loss after spinal cord injury Introduction Dysfunction of vascular system The reduced blood supply of spinal cord Intraparenchymal hemorrhages Spinal cord edema Raised intraspinal pressure Breakdown of BSCB The inflammatory response and elimination of necrotic debris Development of cysts/cavities and syrinx The post-traumatic spinal cord shrinkage Applications to other areas of neuroscience Mini-dictionary of terms Key facts of post-traumatic loss of spinal cord tissue Summary points References Chapter 17: Remodeling mitochondrial transport and cellular energetics in axonal regeneration and spinal cord injury Introduction Complex motility patterns of axonal mitochondria Molecular motors driving mitochondrial bi-directional transport in axons Mitochondrial motor adaptors and receptors Declined axonal mitochondrial transport in mature neurons SNPH immobilizes axonal mitochondria in mature neurons and adult brains Deleting SNPH anchoring boosts axon regeneration in vitro and in vivo Enhanced mitochondrial transport facilitates axon regeneration Remodeling mitochondrial transport promotes regeneration after SCI Boosting energetic metabolism promotes regeneration after SCI Conclusions and new challenges Applications to other areas of neuroscience Mini-dictionary of terms Key facts of SNPH-mediated decline of axonal mitochondrial transport in mature neurons Key facts of the energy crisis that accounts for regeneration failure Key facts of boosting local energy supply in injured axons Summary points References Chapter 18: Neurotrophins and their role in axonal outgrowth following spinal cord injury Introduction Structure and function of the neurotrophins Nerve growth factor Brain-derived neurotrophic factor Neurotrophin-3 Neurotrophin-4/5 Neurotrophic gradients for guiding regenerating axons Preclinical models of neurotrophin delivery to promote axonal outgrowth and regeneration following SCI Acute localized injections and continuous infusions Ex-vivo gene therapy In vivo gene therapy Biomaterial-based approaches Challenges and considerations for neurotrophin delivery and clinical translation Concluding remarks Applications to other areas of neuroscience Mini-dictionary of terms Key facts of neurotrophins in spinal cord injury Summary points References Chapter 19: The neuroscience of transient receptor potential vanilloid type 4 (TRPV4) and spinal cord injury Introduction Transient receptor potential vanilloid type 4 (TRPV4) Spinal cord injury TRPV4 and spinal cord injury TRPV4 role in non-injured conditions Applications to other areas of neuroscience Mini-dictionary of terms Key facts about SCI Key facts about TRPV4 Summary points References Chapter 20: Autoantibodies in spinal cord injury Introduction Targets and possible origin of autoantibodies increased after SCI in humans The levels of autoantibodies after SCI are independent of lesion level and severity Autoantibodies increased after SCI target both CNS and peripheral antigens Local versus systemic production of autoantibodies Association of autoantibodies with neuropathic pain development Roles of the autoantibodies increased after SCI in other pathologies Applications to other areas of neuroscience Mini-dictionary of terms Key facts of autoantibodies Summary points References Chapter 21: Calpain role in the pathophysiology of spasticity after spinal cord injury Introduction Spasticity after spinal cord injury (SCI) Animal models of spasticity after SCI Network alterations contributing to spasticity after SCI Cellular and molecular alterations contributing to spasticity after SCI Calpains and their role in spasticity after SCI Calpain expression and activity after SCI Identified and putative calpain targets involved in the pathophysiology of spasticity Physiological and pharmacological inhibition of calpains and effects on spasticity Applications to other areas of neuroscience Mini-dictionary of terms Key facts of ``spinal hyperexcitability´´ Key facts of ``spinal disinhibition´´ Summary points References Chapter 22: Targeting mTOR signaling to promote autophagy for functional recovery after spinal cord injury Introduction Natural compounds for inhibition of mTOR signaling and promotion of autophagy flux and functional recovery after SCI Curcumin Resveratrol Salidroside Scopoletin Pharmacological inhibition of mTOR signaling for enhancing autophagy flux and functional recovery following SCI Rapamycin Metformin Liraglutide Simvastatin Probucol Genetic and non-genetic inhibitors of mTOR signaling to regulate autophagy in SCI miR-223 Intermittent fasting Future directions Applications to other areas of neuroscience Mini-dictionary of terms Key facts of targeting mTOR signaling in promotion of autophagy for functional recovery after SCI Summary points References Chapter 23: Tertiary damage: Hippocampal and brain changes after spinal cord injury Introduction Sensorimotor cortex and corticospinal tract alterations after SCI in humans Cognitive and emotional impairment after SCI Humans Animal models The effect of SCI on the hippocampus Hippocampal neurons Neurogenesis Neurogenesis during the acute phase Neurogenesis during the chronic phase Hippocampal neuroinflammation Glial reaction during the acute phase Glial reaction during the chronic phase SCI and other brain regions Possible mechanisms underlying the tertiary damage Applications to other areas of neuroscience Mini-dictionary of terms Key facts of tertiary damage Summary points References Section C: Physiological and metabolic effects Chapter 24: Hormonal events and spinal cord injury: A focus on vasopressin and natriuretic peptide Introduction Function of vasopressin (AVP) Function of natriuretic peptides (NP) SCI-induced polyuria/nocturia AVP after SCI ANP after SCI Potential mechanisms causing changes in AVP and/or ANP after SCI Applications to other areas of neuroscience Mini-dictionary of terms Key facts of vasopressin and natriuretic peptide changes after SCI Summary points References Chapter 25: Linking sensorimotor plasticity, the motor cortex, and spinal cord injury Sensorimotor plasticity after spinal cord injury Functional evaluation of motor cortex TMS mapping studies Single-pulse TMS Paired-pulse TMS and paired associative stimulation Discussion Applications to other areas of neuroscience Key facts Mini-dictionary of terms Summary points References Chapter 26: Bone loss at the knee after spinal cord injury: Radiographic imaging, fracture risk, and treatment Introduction Application to other areas of neuroscience Bone loss at the knee after SCI 2D DXA imaging Volumetric assessment of bone mineral and bone strength Summary of bone loss after SCI-Temporal and spatial patterns Relationship between bone loss and fracture risk after SCI Interventions for bone loss after SCI Non-pharmaceutical intervention Pharmaceutical intervention Summary of interventions for bone loss after SCI Summary and conclusions Mini-dictionary terms Key facts Summary points References Chapter 27: Functional and morphological reorganization of the brain following spinal cord injury: Insights from MRI Introduction Brain morphometry Diffusion tensor imaging (DTI) Functional MRI (fMRI) MR spectroscopy Structural reorganization-Insights from MRI Functional reorganization-Insights from MRI Functional MRI (fMRI) studies Resting-state fMRI studies MR spectroscopy Structural and functional reorganization-Insights from MRI Mechanisms underlying reorganization Challenges related to MRI evaluation of SCI data Applications to other areas of neuroscience Mini-dictionary of terms Key facts Summary points References Chapter 28: Cardiometabolic changes and upper exercise as an augmentative strategy in spinal cord injury Introduction Application to other areas of neuroscience Main narrative text Role of inflammation Cardiometabolic changes Cardiovascular disease Body composition Lipid disorders Cardiometabolic syndrome Peripheral vascular regulation Role of exercise as a mitigating treatment Mini-dictionary of terms Key facts: Cardiometabolic changes and exercise in SCI Summary points References Chapter 29: Electrophysiological outcome measures in spinal cord injury: A new narrative Introduction Electromyography (EMG) Research application Reflex EMG activity Evoked potentials Somatosensory evoked potentials (SSEPs) Research application Motor evoked potentials (MEPs) Research application Contact heat evoked potentials (CHEPs) H-reflex Research application Nerve conduction studies (NCS) Research application Silent period (SP) Sympathetic skin response (SSR) Research application Discussion Applications to other areas of neuroscience Key facts of electrophysiological measures Summary points References Chapter 30: Features and physiology of spinal stretch reflexes in people with chronic spinal cord injury Introduction Spinal stretch reflexes Function of the soleus stretch reflex pathways in intact human locomotion Features of spinal stretch reflexes in people with SCI Soleus stretch reflexes during locomotion in people with chronic incomplete SCI Stretch reflexes in spastic gait after SCI Consideration of CNS plasticity in addressing the reflex hyperexcitability in chronic SCI Conclusion Applications to other areas of neuroscience Mini-dictionary of terms Key facts of spinal reflexes Summary points References Chapter 31: Metabolic syndrome in spinal cord injury: Impact on health Introduction Changes in body composition after spinal cord injury Insulin resistance in spinal cord injury: Pathophysiology and clinical features Diagnostic challenges of metabolic syndrome in people with spinal cord injury Cardiovascular reflections of metabolic syndrome in spinal cord injury Pathophysiology of androgen deficiency in men with chronic spinal cord injury Correlates of androgen deficiency in chronic spinal cord injury Applications to other areas of neuroscience Mini-dictionary of terms Key facts of metabolic syndrome in spinal cord injury: Impact on health Summary points References Chapter 32: Body composition and spinal cord injury Introduction Body composition Body composition changes following traumatic spinal cord injury Sarcopenia and SCI Body composition assessment Bedside and field methods Anthropometry Weight and height Body mass index Waist circumference Skinfolds and circumferences Bioelectrical impedance Ultrasound Laboratory and research methods Tracer dilution Air-displacement plethysmograph Imaging techniques Dual-energy X-ray absorptiometry Magnetic resonance imaging Computed tomography Peripheral quantitative computer tomography Novel technique Computerized digital image analysis Summary of body composition assessment methods Choosing a body composition method for use in SCI Applications to other areas of neuroscience Key facts Mini-dictionary of terms Summary points References Chapter 33: Energy requirements and spinal cord injury Introduction Energy expenditure Energy expenditure following SCI Methods for determining energy requirements Doubly labeled water Indirect calorimetry Predictive equations Predictive equations validated in SCI Choosing an energy requirement method for use in SCI Applications to other areas of neuroscience Mini-dictionary of terms Key facts of energy metabolism Summary points References Chapter 34: Virtual walking and spinal cord injury neuropathic pain Introduction SCI-related neuropathic pain as a deafferentation pain Mirror therapy: A precursor to virtual walking What is VR? Non- or partially-immersive virtual walking in SCI Immersion, embodiment, and interactivity Applications to other areas of neuroscience Mini-dictionary of terms Key facts of virtual walking and spinal cord injury neuropathic pain Key facts of SCI neuropathic pain Key facts of VR use for SCI neuropathic pain Summary points References Chapter 35: Cervical spinal cord injury and thermoregulatory processes: A new narrative Introduction Homeostasis Thermoregulatory process in able-bodied individuals Differences between healthy individuals and cSCI patients Alterations in the body composition and energy expenditure after cSCI Alterations in the cardiovascular system after cSCI Disruption in the vasomotor, sudomotor, and shivering responses after cSCI Alterations in the blood pressure after cSCI Applications to other areas of neuroscience Mini-dictionary of terms Key facts of spinal cord injury Key facts of American Spinal Injury Association Summary points References Chapter 36: Spinal cord injury and the gut microbiota Introduction Spinal cord injury-induced dysautonomia Gut dysbiosis after SCI: Pre-clinical studies Gut dysbiosis after SCI: Clinical studies Demographic factors (injury level, injury completeness, age, sex) Gut dysbiosis and health/disease after SCI Mini-dictionary of terms Key facts of the gut microbiome Summary points References Section D: Behavioral and psychological effects Chapter 37: Risk factors and predictors of depression after spinal cord injury: Emphasis on the inflammatory process Introduction Pathophysiological overview: From local inflammation to systemic inflammation after SCI Depression and spinal cord injury Epidemiology, assessment, and risk factors of depression after SCI Etiological factors for depression: The role of inflammation Inflammatory aspects of depression after SCI Conclusion Applications to other areas of neuroscience Mini-dictionary of terms Key facts of depression Summary points References Chapter 38: Spirituality, hope, and resilience in the recovery and adaptation process following spinal cord injury Introduction Responses to trauma: The quest narrative and the role of spirituality, hope, and resilience Spirituality after SCI Hope after SCI Resilience after SCI The relationship between spirituality, hope, and resilience after SCI Implications for SCI rehabilitation: Person-centered care that embraces spirituality, hope, and resilience Applications to other areas of neuroscience Mini-dictionary of terms Key facts of ``Spirituality, hope, and resilience in the recovery and adaptation process following spinal cord injury´´ Summary points References Chapter 39: Wellness intervention for persons with spinal cord injury Introduction What is wellness? Measurement of wellness in SCI Health behaviors: Targets for wellness interventions Behavior change theory for supporting behavior change interventions in SCI Exemplar wellness interventions for persons with SCI: Examples, settings, and results Design of future wellness interventions for persons with SCI Applications to other areas of neuroscience Mini-dictionary of terms Key facts of wellness interventions Summary points References Chapter 40: Sexual life in individuals with spinal cord injury and management Introduction Sexual life in men with SCI Physiology of normal sexual function Parasympathetic innervation Sympathetic innervation Neurophysiology of erection Ejaculation Problems affecting sexual life in men with SCI Erectile dysfunction in men with SCI Ejaculation disorders in men with SCI Orgasm in men with SCI Semen abnormalities and infertility Management of sexual problems in men with SCI Treatment of erectile dysfunction Phosphodiesterase 5-inhibitors (PDE5-Is) Intracavernous injections (ICI) Intraurethral medication Vacuum device and penile rings Penile prostheses Ejaculation dysfunction treatment Penile vibrator stimulation Electroejaculation Prostate massage (PM) Surgical sperm retrieval Psychological support Sex life in women with SCI Problems affecting sexual life in women with SCI and their management Difficulty in genital arousal Orgasm Position problems Psychosocial problems Bowel and bladder incontinence Fertility Birth control Pregnancy Conclusion Applications to other areas of neuroscience Mini-dictionary of terms Key facts of sexual life in individuals with SCI and management Summary points References Chapter 41: Depressive symptoms in rehabilitation post-spinal cord injury Introduction Screening and assessment of depression post-SCI Theoretical correlates of depression post-SCI Management of depression post-SCI Pharmacological Non-pharmacological Applications to other areas of neuroscience Mini-dictionary of terms Key facts of screening and diagnosis Key facts of management Summary points References Chapter 42: Self-harm behaviors in patients with spinal cord injuries: From non-adherence to suicide Introduction Self-harm behaviors and suicidal behaviors Chapter clarifications Self-harm behaviors as presenting symptoms Adapting to disability Depression Existential (palliative/hospice) Medical mistrust Patient preferences Suicide behaviors and SCI Risk mitigation Warning signs for suicide What to assess Social isolation Reduce access to lethal means Applications to other areas of neuroscience Suicide mitigation safety planning for all populations Conclusion Mini-dictionary of terms Key facts of self-harm Summary points References Index Back Cover