Plasticity in the Regenerating Nervous System of the Lamprey, a “Simple” Vertebrate

2018 ◽  
Author(s):  
William Rodemer ◽  
Jianli Hu ◽  
Michael E. Selzer
Keyword(s):  
Spinal Cord ◽  
Nervous System ◽  
Axon Regeneration ◽  
Test Bed ◽  
Human Spinal Cord ◽  
Human Genes ◽  
Cord Injury ◽  
The Face ◽  
Descending Input ◽  
Severed Axons

Human spinal cord injury (SCI) results in long-lasting disabilities due to the failure of damaged neurons to regenerate. The barriers to axon regeneration in mammalian central nervous system (CNS) are so great, and the anatomy so complex that incremental changes in regeneration brought about by pharmacological or molecular manipulations can be difficult to demonstrate. By contrast, lampreys recover functionally after a complete spinal cord transection (TX), based on regeneration of severed axons, even though lampreys share the basic organization of the mammalian CNS, including many of the same molecular barriers to regeneration. And because the regeneration is incomplete, it can be studied by manipulations designed to either inhibit or enhance it. In the face of reduced descending input, recovery of swimming and other locomotor functions must be accompanied by compensatory remodeling throughout the CNS, as would be required for functional recovery in mammals. For such studies, lampreys have significant advantages. They have several large, identified reticulospinal (RS) neurons, whose regenerative abilities have been individually quantified. Other large neurons and axons are visible in the spinal cord and can be impaled with microelectrodes under direct microscopic vision. The central pattern generator for locomotion is exceptionally well-defined, and is subject to significant neuromodulation. Finally, the lamprey genome has been sequenced, so that molecular homologs of human genes can be identified and cloned. Because of these advantages, the lamprey spinal cord has been a fertile source of information about the biology of axon regeneration in the vertebrate CNS, and has the potential to serve as a test bed for the investigation of novel therapeutic approaches to SCI and other CNS injuries.

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 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 Geoffrey Raisman. 28 June 1939—27 January 2017

2018 ◽  
Vol 65 ◽  
pp. 341-355
Author(s):  
James Fawcett
Keyword(s):  
Spinal Cord ◽  
Nervous System ◽  
Glial Cells ◽  
Spinal Cord Injuries ◽  
Axon Regeneration ◽  
Scar Tissue ◽  
Human Spinal Cord ◽  
New Energy ◽  
Spinal Cord Repair ◽  
The Brain

Geoffrey Raisman was a neuroscientist whose particular love was the microanatomy and ultrastructure of the nervous system. From his anatomical studies came discoveries in synaptic plasticity, neuroendocrinology, axon regeneration, spinal cord repair and glaucoma. His studies of the anatomy of synapses after denervation led to his concept of plasticity, where synapses compete for targets and can replace those that are lost. This discovery persuaded him, against the dominant view of the time, that some repair of the damaged nervous system should be possible. His studies of the events following damage to the nervous system led to the pathway hypothesis; axon regeneration is blocked by scar tissue formed of glial cells around injuries. Finding that the newly born olfactory neurons that are created throughout life grow axons into the brain with the assistance of specialized olfactory glia, he realized that these glial cells might also assist regenerating axons to bridge the scar tissue blocking axon regeneration. Preliminary trials of this treatment in human spinal cord injuries have shown some clinical promise. He recently developed a new energy theory of glaucoma.

Spinal Cord Injuries the Facts of Neuropathology: Opportunities and Limitations

2019 ◽  
Vol 1 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Byron A Kakulas
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Wallerian Degeneration ◽  
Spinal Cord Injuries ◽  
Neurological Status ◽  
Research Projects ◽  
Human Spinal Cord ◽  
The Third ◽  
Cord Injury

It is essential for research projects which are undertaken to find a “cure” for human spinal cord injury (SCI) to be consistent with the neuropathological facts of the disorder. In this respect there are three main points to be taken into account. Firstly, the researcher should be aware that simple transection of the spinal cord is not a feature of human SCI. The usual lesion is one of compression and disruption with haemorrhage. The second and most important aspect of human SCI is to understand that Wallerian degeneration inevitably ensues following disruption of the axon. Wallerian degeneration is progressive and inexorable and unlike the peripheral nervous system CNS axons do not regenerate. The third and more helpful fact is that in the majority (71%) of SCI autopsies a small amount of white matter, myelin and axons, was found to be preserved at the level of injury. Re-activation of these dormant, axons offers the opportunity for improvement of the SCI patient’s neurological status by means of restorative neurology (RN).

Olfactory Ensheathing Cells: Bridging the Gap in Spinal Cord Injury

Neurosurgery ◽  
2000 ◽  
Vol 47 (5) ◽  
pp. 1057-1069 ◽  
Author(s):  
Juan C. Bartolomei ◽  
Charles A. Greer
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Axon Regeneration ◽  
Therapeutic Interventions ◽  
Olfactory Ensheathing Cells ◽  
Therapeutic Window ◽  
Secondary Injury ◽  
Cord Injury ◽  
Ensheathing Cells

Abstract SPINAL CORD INJURY (SCI) continues to be an insidious and challenging problem for scientists and clinicians. Recent neuroscientific advances have changed the pessimistic notion that axons are not capable of significant extension after transection. The challenges of recovering from SCI have been broadly divided into four areas: 1) cell survival; 2) axon regeneration (growth); 3) correct targeting by growing axons; and 4) establishment of correct and functional synaptic appositions. After acute SCI, there seems to be a therapeutic window of opportunity within which the devastating consequences of the secondary injury can be ameliorated. This is supported by several observations in which apoptotic glial cells have been identified up to 1 week after acute SCI. Moreover, autopsy studies have identified anatomically preserved but unmyelinated axons that could potentially subserve normal physiological properties. These observations suggest that therapeutic strategies after SCI can be directed into two broad modalities: 1) prevention or amelioration of the secondary injury, and 2) restorative or regenerative interventions. Intraspinal transplants have been used after SCI as a means for restoring the severed neuraxis. Fetal cell transplants and, more recently, progenitor cells have been used to restore intraspinal circuitry or to serve as relay for damaged axons. In an attempt to remyelinate anatomically preserved but physiologically disrupted axons, newer therapeutic interventions have incorporated the transplantation of myelinating cells, such as Schwann cells, oligodendrocytes, and olfactory ensheathing cells. Of these cells, the olfactory ensheathing cells have become a more favorable candidate for extensive remyelination and axonal regeneration. Olfactory ensheathing cells are found along the full length of the olfactory nerve, from the basal lamina of the epithelium to the olfactory bulb, crossing the peripheral nervous system-central nervous system junction. In vitro, these cells promote robust axonal growth, in part through cell adhesion molecules and possibly by secretion of neurotrophic growth factors that support axonal elongation and extension. In animal models of SCI, transplantation of ensheathing cells supports axonal remyelination and extensive migration throughout the length of the spinal cord. Although the specific properties of these cells that govern enhanced axon regeneration remain to be elucidated, it seems certain that they will contribute to the establishment of new horizons in SCI research.

scholarly journals Updates and challenges of axon regeneration in the mammalian central nervous system

2020 ◽  
Author(s):  
Cheng Qian ◽  
Feng-Quan Zhou
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Axon Regeneration ◽  
Axon Growth ◽  
Research Progress ◽  
Regeneration Ability ◽  
Long Distance ◽  
Mammalian Central Nervous System ◽  
Cord Injury

Abstract Axon regeneration in the mammalian central nervous system (CNS) has been a long-standing and highly challenging issue. Successful CNS axon regeneration will benefit many human diseases involving axonal damage, such as spinal cord injury, traumatic brain injury, glaucoma, and neurodegenerative diseases. The current consensus is that the diminished intrinsic regenerative ability in mature CNS neurons and the presence of extrinsic inhibitors blocking axon regrowth are two major barriers for axon regeneration. During the past decade, studies targeting the intrinsic axon growth ability via regulation of gene transcription have produced very promising results in optic nerve and/or spinal cord regeneration. Manipulations of various signaling pathways or the nuclear transcription factors directly have been shown to sufficiently drive CNS axon regrowth. Converging evidence reveals that some pro-regenerative transcriptomic states, which are commonly accomplished by more comprehensive epigenetic regulations, exist to orchestrate the complex tasks of injury sensing and axon regeneration. Moreover, genetic reprogramming achieved via transcriptome and epigenome modifications provides novel mechanisms for enhancing axon regeneration. Recent studies also highlighted the important roles of remodeling neuronal cytoskeleton in overcoming the extrinsic inhibitory cues. However, our knowledge about the cellular and molecular mechanisms by which neurons regulate their intrinsic axon regeneration ability and response to extrinsic inhibitory cues is still fragmented. Here, we provide an update about recent research progress in axon regeneration and discuss major remaining challenges for long-distance axon regeneration and the subsequent functional recovery.

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