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Clinical and Experimental Pharmacology... Jul 20001. The adult mammalian central nervous system (CNS) is unable to regenerate following injury and repair has only been seen when implants of peripheral nervous tissue,... (Review)
Review
1. The adult mammalian central nervous system (CNS) is unable to regenerate following injury and repair has only been seen when implants of peripheral nervous tissue, fetal tissue or Schwann cells are used, or antibodies or trophic molecules applied. However, the immature mammalian CNS has revealed a capacity to repair without extrinsic influence. 2. The marsupial mammal provides a unique opportunity to access the immature CNS without invasive in utero surgery. In particular, the South American opossum Monodelphis domestica is an ideal animal for spinal cord injury studies examining the ability of the immature CNS to repair after injury. 3. The Monodelphis spinal cord may be examined for its response to injury either as an in vitro or in vivo system and, therefore, is a flexible model, allowing many different questions to be addressed by the most suitable approach. 4. The immature Monodelphis CNS was able to support fibre growth that reappeared 4 days after a crush at P3-P8 in vitro. Conduction was also restored at this time, accompanied by synaptic connections. 5. A cut lesion performed in vivo on Monodelphis spinal cords at P7 took longer to repair, with fibres reappearing across the injury site 2 weeks after the lesion; greater disruption to structure was noted both during early stages of repair and in adulthood. 6. Neural pathway tracing with dextran amine from the lumbar cord to the brain in adult Monodelphis, which received spinal lesions at P7, revealed a similar distribution of labelled cells in brainstem and mid-brain nuclei to that of control animals. 7. Studies of the locomotor behaviour of adult Monodelphis that had received either a cut or crush lesion at P7-P8 showed remarkably similar abilities to control animals when performing complex tasks. 8. The results of spinal cord injury studies with the immature Monodelphis CNS may help in the development of treatments for spinal injury patients.
Topics: Animals; Nerve Crush; Nerve Regeneration; Neural Pathways; Opossums; Spinal Cord; Spinal Cord Injuries
PubMed: 10874515
DOI: 10.1046/j.1440-1681.2000.03296.x -
PloS One 2011Forging a relationship between progenitors with dynamically changing gene expression and their terminal fate is instructive for understanding the logic of how cell-type...
BACKGROUND
Forging a relationship between progenitors with dynamically changing gene expression and their terminal fate is instructive for understanding the logic of how cell-type diversity is established. The mouse spinal cord is an ideal system to study these mechanisms in the context of developmental genetics and nervous system development. Here we focus on the Gastrulation homeobox 2 (Gbx2) transcription factor, which has not been explored in spinal cord development.
METHODOLOGY/PRINCIPAL FINDINGS
We determined the molecular identity of Gbx2-expressing spinal cord progenitors. We also utilized genetic inducible fate mapping to mark the Gbx2 lineage at different embryonic stages in vivo in mouse. Collectively, we uncover cell behaviors, cytoarchitectonic organization, and the terminal cell fate of the Gbx2 lineage. Notably, both ventral motor neurons and interneurons are derived from the Gbx2 lineage, but only during a short developmental period. Short-term fate mapping during mouse spinal cord development shows that Gbx2 expression is transient and is extinguished ventrally in a rostral to caudal gradient. Concomitantly, a permanent lineage restriction boundary ensures that spinal cord neurons derived from the Gbx2 lineage are confined to a dorsal compartment that is maintained in the adult and that this lineage generates inhibitory interneurons of the spinal cord. Using lineage tracing and molecular markers to follow Gbx2-mutant cells, we show that the loss of Gbx2 globally affects spinal cord patterning including the organization of interneuron progenitors. Finally, long-term lineage analysis reveals that the presence and timing of Gbx2 expression in interneuron progenitors results in the differential contribution to subtypes of terminally differentiated interneurons in the adult spinal cord.
CONCLUSIONS/SIGNIFICANCE
We illustrate the complex cellular nature of Gbx2 expression and lineage contribution to the mouse spinal cord. In a broader context, this study provides a direct link between spinal cord progenitors undergoing dynamic changes in molecular identity and terminal neuronal fate.
Topics: Animals; Cell Lineage; Homeodomain Proteins; Mice; Spinal Cord
PubMed: 21698205
DOI: 10.1371/journal.pone.0020940 -
Paraplegia Apr 1989In the last 2 decades, the application of new techniques in neuroanatomy has led to spectacular advances in our knowledge of the structure and function of the human... (Review)
Review
In the last 2 decades, the application of new techniques in neuroanatomy has led to spectacular advances in our knowledge of the structure and function of the human spinal cord. In 1988, it is appropriate to review this progress, and I am grateful to Sir George Bedbrook and the organisers of the International Paraplegia Meeting in Perth, Western Australia, for inviting me to give this survey, to which I have given the title 'The New Neuroanatomy of the Spinal Cord'.
Topics: Antibodies, Monoclonal; Humans; Neurochemistry; Neurology; Neuropeptides; Spinal Cord
PubMed: 2654822
DOI: 10.1038/sc.1989.15 -
Current Opinion in Neurobiology Dec 1991Sensory gating mechanisms are deployed during vertebrate locomotion to ensure that adaptive and appropriate motor responses to afferent input occur during all phases of... (Review)
Review
Sensory gating mechanisms are deployed during vertebrate locomotion to ensure that adaptive and appropriate motor responses to afferent input occur during all phases of the movement cycle. Recent animal studies on the integration of cutaneous information have investigated the roles of interneurones in sensory gating. Premotor interneurones, rhythmically active during locomotion, as well as 'sensory' interneurones appear to be intimately involved in sensory gating, receiving synaptic inputs from the spinal rhythm generator to gate the flow of sensory information in the spinal cord.
Topics: Animals; Humans; Nerve Net; Neurons, Afferent; Spinal Cord
PubMed: 1822300
DOI: 10.1016/s0959-4388(05)80032-7 -
Neuropediatrics Jun 2020
Topics: Child; Female; Humans; Magnetic Resonance Imaging; Neural Tube Defects; Spinal Cord
PubMed: 31752028
DOI: 10.1055/s-0039-3399530 -
The Journal of Neuroscience : the... Dec 1996At early neural tube stages, individual stem cells can generate neural crest cells as well as dorsal or ventral spinal cord cells. To determine whether this pluripotency...
At early neural tube stages, individual stem cells can generate neural crest cells as well as dorsal or ventral spinal cord cells. To determine whether this pluripotency is lost as development proceeds, we back-transplanted quail spinal cells from different developmental stages and different spinal locations into the crest migratory pathways of st 16-20 chicken host embryos. The transplanted spinal cells from st 27 dorsal cord and st 18 ventral cord differentiated within the new crest environment into sensory and sympathetic neurons, satellite and Schwann cells, and melanocytes. St 27 ventral cells still generated several crest derivatives but not sensory or sympathetic neurons. This loss in ability to produce neurons correlates with the end of neurogenesis in ventral cord. The end of neurogenesis in the cord, therefore, results from an intrinsic change in the potential of spinal neuroepithelial cells to generate neurons.
Topics: Animals; Cell Differentiation; Cell Division; Cell Movement; Cell Transplantation; Chick Embryo; Embryonic and Fetal Development; Fetal Tissue Transplantation; Neural Crest; Spinal Cord; Tissue Donors
PubMed: 8922420
DOI: 10.1523/JNEUROSCI.16-23-07638.1996 -
Bioelectromagnetics Dec 2015The prime goal of this work was to model essentially steady (DC) fields from electrodes, implanted in several ways, which have been suggested as possible means to...
The prime goal of this work was to model essentially steady (DC) fields from electrodes, implanted in several ways, which have been suggested as possible means to encourage nerve fiber regrowth in spinal cord injuries. A simplified model of the human spinal cord in the lumbar region and the SEMCAD-X computer program were used to calculate electric field and current density patterns from electrodes outside vertebrae and those inserted extradurally within the spinal canal. DC electric fields guide nerve growth in developing organisms and in vitro. They also have been shown to encourage healing of injured peripheral nerves, and application of a longitudinal field has been used in attempts to bridge spinal cord injuries. When calculated results are scaled to the experimental level used in the literature, all modeled electrodes produced fields in the spinal cord below fields needed in the literature for stimulation of spinal as well as peripheral nerve growth in vitro, in dogs, and in a published clinical human trial. The highly-conducting cerebrospinal fluid appeared to provide effective shielding; there was also a very high degree of polarization at electrodes.
Topics: Electric Stimulation; Electrodes, Implanted; Electrophysiological Phenomena; Humans; Models, Anatomic; Neurites; Spinal Cord; Spinal Cord Injuries
PubMed: 26525912
DOI: 10.1002/bem.21940 -
Proceedings of the National Academy of... May 2024We report the reliable detection of reproducible patterns of blood-oxygenation-level-dependent (BOLD) MRI signals within the white matter (WM) of the spinal cord during...
We report the reliable detection of reproducible patterns of blood-oxygenation-level-dependent (BOLD) MRI signals within the white matter (WM) of the spinal cord during a task and in a resting state. Previous functional MRI studies have shown that BOLD signals are robustly detectable not only in gray matter (GM) in the brain but also in cerebral WM as well as the GM within the spinal cord, but similar signals in WM of the spinal cord have been overlooked. In this study, we detected BOLD signals in the WM of the spinal cord in squirrel monkeys and studied their relationships with the locations and functions of ascending and descending WM tracts. Tactile sensory stimulus -evoked BOLD signal changes were detected in the ascending tracts of the spinal cord using a general-linear model. Power spectral analysis confirmed that the amplitude at the fundamental frequency of the response to a periodic stimulus was significantly higher in the ascending tracts than the descending ones. Independent component analysis of resting-state signals identified coherent fluctuations from eight WM hubs which correspond closely to the known anatomical locations of the major WM tracts. Resting-state analyses showed that the WM hubs exhibited correlated signal fluctuations across spinal cord segments in reproducible patterns that correspond well with the known neurobiological functions of WM tracts in the spinal cord. Overall, these findings provide evidence of a functional organization of intraspinal WM tracts and confirm that they produce hemodynamic responses similar to GM both at baseline and under stimulus conditions.
Topics: Animals; White Matter; Spinal Cord; Magnetic Resonance Imaging; Saimiri; Rest; Oxygen; Male; Gray Matter; Female
PubMed: 38776372
DOI: 10.1073/pnas.2316117121 -
Journal of Visualized Experiments : JoVE May 2018Selective manipulation of spinal neuronal subpopulations has mainly been achieved by two different methods: 1) Intersectional genetics, whereby double or triple...
Selective manipulation of spinal neuronal subpopulations has mainly been achieved by two different methods: 1) Intersectional genetics, whereby double or triple transgenic mice are generated in order to achieve selective expression of a reporter or effector gene (e.g., from the Rosa26 locus) in the desired spinal population. 2) Intraspinal injection of Cre-dependent recombinant adeno-associated virus (rAAV); here Cre-dependent AAV vectors coding for the reporter or effector gene of choice are injected into the spinal cord of mice expressing Cre recombinase in the desired neuronal subpopulation. This protocol describes how to generate Cre-dependent rAAV vectors and how to transduce neurons in the dorsal horn of the lumbar spinal cord segments L3-L5 with rAAVs. As the lumbar spinal segments L3-L5 are innervated by those peripheral sensory neurons that transmit sensory information from the hindlimbs, spontaneous behavior and responses to sensory tests applied to the hindlimb ipsilateral to the injection side can be analyzed in order to interrogate the function of the manipulated neurons in sensory processing. We provide examples of how this technique can be used to analyze genetically defined subsets of spinal neurons. The main advantages of virus-mediated transgene expression in Cre transgenic mice compared to classical reporter mouse-induced transgene expression are the following: 1) Different Cre-dependent rAAVs encoding various reporter or effector proteins can be injected into a single Cre transgenic line, thus overcoming the need to create several multiple transgenic mouse lines. 2) Intraspinal injection limits manipulation of Cre-expressing cells to the injection site and to the time after injection. The main disadvantages are: 1) Reporter gene expression from rAAVs is more variable. 2) Surgery is required to transduce the spinal neurons of interest. Which of the two methods is more appropriate depends on the neuron population and research question to be addressed.
Topics: Adenoviridae; Animals; Genetic Therapy; Mice; Mice, Transgenic; Spinal Cord; Transgenes
PubMed: 29806830
DOI: 10.3791/57382 -
Journal of Magnetic Resonance Imaging :... May 2005To develop a spinal functional MRI (fMRI) method with three-dimensional coverage of a large extent of the spinal cord with minimal partial volume effects
PURPOSE
To develop a spinal functional MRI (fMRI) method with three-dimensional coverage of a large extent of the spinal cord with minimal partial volume effects
MATERIALS AND METHODS
fMRI data of the cervical spinal cord were obtained at 1.5 T with a single-shot fast spin-echo imaging method, from thin contiguous sagittal slices spanning the cord. Thermal stimulation was applied to the palm of the hand in a block pattern with 15 degrees C for stimulation and 32 degrees C during baseline periods. Prior to analysis, the image data at each time point were reformatted into three-dimensional volumes and resliced perfectly transverse to the spinal cord. Smoothing was applied only in the superior-inferior (S/I) direction across uniform tissue types. Active voxels were then identified by means of a correlation to a model paradigm.
RESULTS
The resulting activity maps demonstrate activity primarily in ipsilateral sensory areas and in some motor areas, consistent with the spinal cord neuroanatomy. These data also demonstrate detail of the subsegmental organization of the spinal cord, as well as anatomical detail of the spinous processes and positions of nerve roots.
CONCLUSION
The spinal fMRI method described enables large volume coverage of the spinal cord in three dimensions, with reliable and reproducible results.
Topics: Humans; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; Magnetic Resonance Imaging; Spinal Cord
PubMed: 15834915
DOI: 10.1002/jmri.20315