scholarly journals Long-term in vivo imaging of mouse spinal cord through an optically cleared intervertebral window

2021 ◽  
Author(s):  
Wanjie Wu ◽  
Sicong He ◽  
Junqiang Wu ◽  
Congping Chen ◽  
Xuesong Li ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Nervous System ◽  
Stimulated Raman Scattering ◽  
Minimal Invasive ◽  
Mouse Spinal Cord ◽  
Cord Injury ◽  
The Central Nervous System ◽  
Communication Pathway

Spinal cord, as part of the central nervous system, accounts for the main communication pathway between the brain and the peripheral nervous system. Spinal cord injury is a devastating and largely irreversible neurological trauma, and can result in lifelong disability and paralysis with no available cure. In vivo spinal cord imaging in mouse models without introducing immunological artifacts is critical to understand spinal cord pathology and discover effective treatments. We developed a minimal-invasive intervertebral window by retaining ligamentum flavum to protect the underlying spinal cord. By introducing an optical clearing method, we achieved repeated two-photon fluorescence and stimulated Raman scattering imaging at subcellular resolution with up to 16 imaging sessions over 167 days and observed no inflammatory response. Using this optically cleared intervertebral window, we studied the neuron-glia dynamics following laser axotomy and observed strengthened contact of microglia with the nodes of Ranvier during axonal degeneration. By enabling long-term, repetitive, stable, high-resolution and inflammation-free imaging of mouse spinal cord, our method provides a reliable platform in the research aiming at understanding and treatment of spinal cord pathology.

Further studies on free-radical pathology in the major central nervous system disorders: effect of very high doses of methylprednisolone on the functional outcome, morphology, and chemistry of experimental spinal cord impact injury

1982 ◽  
Vol 60 (11) ◽  
pp. 1415-1424 ◽  
Author(s):  
H. B. Demopoulos ◽  
E. S. Flamm ◽  
M. L. Seligman ◽  
D. D. Pietronigro ◽  
J. Tomasula ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Free Radical ◽  
Tissue Injury ◽  
Functional Restoration ◽  
Radical Reactions ◽  
Free Radical Reactions ◽  
Cord Injury

The hypothesis that pathologic free-radical reactions are initiated and catalyzed in the major central nervous system (CNS) disorders has been further supported by the current acute spinal cord injury work that has demonstrated the appearance of specific, cholesterol free-radical oxidation products. The significance of these products is suggested by the fact that: (i) they increase with time after injury; (ii) their production is curtailed with a steroidal antioxidant; (iii) high antioxidant doses of the steroidal antioxidant which curtail the development of free-radical product prevent tissue degeneration and permit functional restoration. The role of pathologic free-radical reactions is also inferred from the loss of ascorbic acid, a principal CNS antioxidant, and of extractable cholesterol. These losses are also prevented by the steroidal antioxidant. This model system is among others in the CNS which offer distinctive opportunities to study, in vivo, the onset and progression of membrane damaging free-radical reactions within well-defined parameters of time, extent of tissue injury, correlation with changes in membrane enzymes, and correlation with readily measurable in vivo functions.

scholarly journals Biomaterial Approaches to Modulate Reactive Astroglial Response

2018 ◽  
Vol 205 (5-6) ◽  
pp. 372-395 ◽  
Author(s):  
Jonathan M. Zuidema ◽  
Ryan J. Gilbert ◽  
Manoj K. Gottipati
Keyword(s):  
Spinal Cord ◽  
Glial Scar ◽  
Secondary Injury ◽  
Injury Site ◽  
Beneficial Effects ◽  
Cord Injury ◽  
The Central Nervous System ◽  
Preclinical Animal Models

Over several decades, biomaterial scientists have developed materials to spur axonal regeneration and limit secondary injury and tested these materials within preclinical animal models. Rarely, though, are astrocytes examined comprehensively when biomaterials are placed into the injury site. Astrocytes support neuronal function in the central nervous system. Following an injury, astrocytes undergo reactive gliosis and create a glial scar. The astrocytic glial scar forms a dense barrier which restricts the extension of regenerating axons through the injury site. However, there are several beneficial effects of the glial scar, including helping to reform the blood-brain barrier, limiting the extent of secondary injury, and supporting the health of regenerating axons near the injury site. This review provides a brief introduction to the role of astrocytes in the spinal cord, discusses astrocyte phenotypic changes that occur following injury, and highlights studies that explored astrocyte changes in response to biomaterials tested within in vitro or in vivo environments. Overall, we suggest that in order to improve biomaterial designs for spinal cord injury applications, investigators should more thoroughly consider the astrocyte response to such designs.

scholarly journals Virtual Reality In Paraplegia: A Test Bed Applicationn

2001 ◽  
Vol 5 (1) ◽  
pp. 146-156
Author(s):  
Giuseppe Riva
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Virtual Reality ◽  
Nervous System ◽  
Design Issues ◽  
Test Bed ◽  
Design Considerations ◽  
Cord Injury ◽  
Preliminary Study

The paper presents an overview of the ergonomic/design issues of a VR-enhanced orthopaedic appliance to be used in rehabilitation of patients with Spinal Cord Injury. First, some design considerations are described and an outline of aims which the tool should pursue are given. Finally, the design issues are described focusing both on the development of a test-bed rehabilitation device and on the description of a preliminary study detailing the use of the device with a long-term SCI patient. The basis for this approach is that physical therapy and motivation are crucial for maintaining flexibility and muscle strength and for reorganizing the nervous system after SCIs.

scholarly journals Growth-Promoting Treatment Screening for Corticospinal Neurons in Mouse and Man

2020 ◽  
Vol 40 (8) ◽  
pp. 1327-1338
Author(s):  
Nicholas Hanuscheck ◽  
Andrea Schnatz ◽  
Carine Thalman ◽  
Steffen Lerch ◽  
Yvonne Gärtner ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Nervous System ◽  
Interleukin 4 ◽  
Regenerative Capacity ◽  
Beneficial Effects ◽  
Cord Injury ◽  
Tissue Culture Model ◽  
The Central Nervous System ◽  
Cone Formation ◽  
New Treatments

Abstract Neurons of the central nervous system (CNS) that project long axons into the spinal cord have a poor axon regenerative capacity compared to neurons of the peripheral nervous system. The corticospinal tract (CST) is particularly notorious for its poor regeneration. Because of this, traumatic spinal cord injury (SCI) is a devastating condition that remains as yet uncured. Based on our recent observations that direct neuronal interleukin-4 (IL-4) signaling leads to repair of axonal swellings and beneficial effects in neuroinflammation, we hypothesized that IL-4 acts directly on the CST. Here, we developed a tissue culture model for CST regeneration and found that IL-4 promoted new growth cone formation after axon transection. Most importantly, IL-4 directly increased the regenerative capacity of both murine and human CST axons, which corroborates its regenerative effects in CNS damage. Overall, these findings serve as proof-of-concept that our CST regeneration model is suitable for fast screening of new treatments for SCI.

scholarly journals Nitrous Oxide Impairs Axon Regeneration after Nervous System Injury in Male Rats

2019 ◽  
Vol 131 (5) ◽  
pp. 1063-1076
Author(s):  
Krista J. Stewart ◽  
Bermans J. Iskandar ◽  
Brenton M. Meier ◽  
Elias B. Rizk ◽  
Nithya Hariharan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Nitrous Oxide ◽  
Folic Acid ◽  
Functional Recovery ◽  
Axon Regeneration ◽  
Retinal Ganglion ◽  
Cord Injury

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Nitrous oxide can induce neurotoxicity. The authors hypothesized that exposure to nitrous oxide impairs axonal regeneration and functional recovery after central nervous system injury. Methods The consequences of single and serial in vivo nitrous oxide exposures on axon regeneration in four experimental male rat models of nervous system injury were measured: in vitro axon regeneration in cell culture after in vivo nitrous oxide administration, in vivo axon regeneration after sharp spinal cord injury, in vivo axon regeneration after sharp optic nerve injury, and in vivo functional recovery after blunt contusion spinal cord injury. Results In vitro axon regeneration 48 h after a single in vivo 70% N2O exposure is less than half that in the absence of nitrous oxide (mean ± SD, 478 ± 275 um; n = 48) versus 210 ± 152 um (n = 48; P < 0.0001). A single exposure to 80% N2O inhibits the beneficial effects of folic acid on in vivo axonal regeneration after sharp spinal cord injury (13.4 ± 7.1% regenerating neurons [n = 12] vs. 0.6 ± 0.7% regenerating neurons [n = 4], P = 0.004). Serial 80% N2O administration reverses the benefit of folic acid on in vivo retinal ganglion cell axon regeneration after sharp optic nerve injury (1277 ± 180 regenerating retinal ganglion cells [n = 7] vs. 895 ± 164 regenerating retinal ganglion cells [n = 7], P = 0.005). Serial 80% N2O exposures reverses the benefit of folic acid on in vivo functional recovery after blunt spinal cord contusion (estimate for fixed effects ± standard error of the estimate: folic acid 5.60 ± 0.54 [n = 9] vs. folic acid + 80% N2O 5.19 ± 0.62 [n = 7], P < 0.0001). Conclusions These data indicate that nitrous oxide can impair the ability of central nervous system neurons to regenerate axons after sharp and blunt trauma.

scholarly journals Acellularized spinal cord scaffolds incorporating bpV(pic)/PLGA microspheres promote axonal regeneration and functional recovery after spinal cord injury

RSC Advances ◽  
2020 ◽  
Vol 10 (32) ◽  
pp. 18677-18686
Author(s):  
Jia Liu ◽  
Kai Li ◽  
Ke Huang ◽  
Chengliang Yang ◽  
Zhipeng Huang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Axonal Regeneration ◽  
Traumatic Injury ◽  
High Rate ◽  
Plga Microspheres ◽  
Cord Injury ◽  
The Central Nervous System

Spinal cord injury (SCI) is a traumatic injury to the central nervous system (CNS) with a high rate of disability and a low capability of self-recovery.

scholarly journals Neuroplasticity After Spinal Cord Injury and Training: An Emerging Paradigm Shift in Rehabilitation and Walking Recovery

2006 ◽  
Vol 86 (10) ◽  
pp. 1406-1425 ◽  
Author(s):  
Andrea L Behrman ◽  
Mark G Bowden ◽  
Preeti M Nair
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Paradigm Shift ◽  
Clinical Findings ◽  
Cord Injury ◽  
Rehabilitation Concepts ◽  
The Central Nervous System ◽  
Walking Recovery ◽  
Physiologically Based Approach

AbstractPhysical rehabilitation after spinal cord injury has been based on the premise that the nervous system is hard-wired and irreparable. Upon this assumption, clinicians have compensated for irremediable sensorimotor deficits using braces, assistive devices, and wheelchairs to achieve upright and seated mobility. Evidence from basic science, however, demonstrates that the central nervous system after injury is malleable and can learn, and this evidence has challenged our current assumptions. The evidence is especially compelling concerning locomotion. The purpose of this perspective article is to summarize the evidence supporting an impending paradigm shift from compensation for deficits to rehabilitation as an agent for walking recovery. A physiologically based approach for the rehabilitation of walking has developed, translating evidence for activity-dependent neuroplasticity after spinal cord injury and the neurobiological control of walking. Advanced by partnerships among neuroscientists, clinicians, and researchers, critical rehabilitation concepts are emerging for activity-based therapy to improve walking recovery, with promising clinical findings.

scholarly journals Zinc Regulates Glucose Metabolism of the Spinal Cord and Neurons and Promotes Functional Recovery after Spinal Cord Injury through the AMPK Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-27
Author(s):  
Hengshuo Hu ◽  
Nan Xia ◽  
Jiaquan Lin ◽  
Daoyong Li ◽  
Chuanjie Zhang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Functional Recovery ◽  
Glucose Metabolism Disorders ◽  
Cord Injury

Spinal cord injury (SCI) is a traumatic disease that can cause severe nervous system dysfunction. SCI often causes spinal cord mitochondrial dysfunction and produces glucose metabolism disorders, which affect neuronal survival. Zinc is an essential trace element in the human body and plays multiple roles in the nervous system. This experiment is intended to evaluate whether zinc can regulate the spinal cord and neuronal glucose metabolism and promote motor functional recovery after SCI. Then we explore its molecular mechanism. We evaluated the function of zinc from the aspects of glucose uptake and the protection of the mitochondria in vivo and in vitro. The results showed that zinc elevated the expression level of GLUT4 and promoted glucose uptake. Zinc enhanced the expression of proteins such as PGC-1α and NRF2, reduced oxidative stress, and promoted mitochondrial production. In addition, zinc decreased neuronal apoptosis and promoted the recovery of motor function in SCI mice. After administration of AMPK inhibitor, the therapeutic effect of zinc was reversed. Therefore, we concluded that zinc regulated the glucose metabolism of the spinal cord and neurons and promoted functional recovery after SCI through the AMPK pathway, which is expected to become a potential treatment strategy for SCI.

scholarly journals Pericyte-derived fibrotic scarring is conserved across diverse central nervous system lesions

2020 ◽  
Author(s):  
David O. Dias ◽  
Jannis Kalkitsas ◽  
Yildiz Kelahmetoglu ◽  
Cynthia P. Estrada ◽  
Jemal Tatarishvili ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Mouse Models ◽  
Stromal Cells ◽  
Primary Source ◽  
Lineage Tracing ◽  
Fibrotic Tissue ◽  
Cord Injury

AbstractFibrotic scar tissue limits central nervous system regeneration in adult mammals. The extent of fibrotic tissue generation and distribution of stromal cells across different lesions in the brain and spinal cord has not been systematically investigated in mice and humans. Furthermore, it is unknown whether scar-forming stromal cells have the same origin throughout the central nervous system and in different types of lesions. In the current study, we compared fibrotic scarring in human pathological tissue and corresponding mouse models of penetrating and non-penetrating spinal cord injury, traumatic brain injury, ischemic stroke, multiple sclerosis and glioblastoma. We show that the extent and distribution of stromal cells are specific to the type of lesion and, in most cases, similar between mice and humans. Employing in vivo lineage tracing, we report that in all mouse models developing fibrotic tissue, the primary source of scar-forming fibroblasts is a discrete subset of perivascular cells, termed type A pericytes.We uncover pericyte-derived fibrosis as a conserved mechanism that may be explored as a therapeutic target to improve recovery after central nervous system lesions.

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