Dynamic Computational Model of the Human Spinal Cord Connectome

2019 ◽  
Vol 31 (2) ◽  
pp. 388-416 ◽  
Author(s):  
Jeffrey E. Arle ◽  
Nicolae Iftimia ◽  
Jay L. Shils ◽  
Longzhi Mei ◽  
Kristen W. Carlson

Connectomes abound, but few for the human spinal cord. Using anatomical data in the literature, we constructed a draft connectivity map of the human spinal cord connectome, providing a template for the many calibrations of specialized behavior to be overlaid on it and the basis for an initial computational model. A thorough literature review gleaned cell types, connectivity, and connection strength indications. Where human data were not available, we selected species that have been studied. Cadaveric spinal cord measurements, cross-sectional histology images, and cytoarchitectural data regarding cell size and density served as the starting point for estimating numbers of neurons. Simulations were run using neural circuitry simulation software. The model contains the neural circuitry in all ten Rexed laminae with intralaminar, interlaminar, and intersegmental connections, as well as ascending and descending brain connections and estimated neuron counts for various cell types in every lamina of all 31 segments. We noted the presence of highly interconnected complex networks exhibiting several orders of recurrence. The model was used to perform a detailed study of spinal cord stimulation for analgesia. This model is a starting point for workers to develop and test hypotheses across an array of biomedical applications focused on the spinal cord. Each such model requires additional calibrations to constrain its output to verifiable predictions. Future work will include simulating additional segments and expanding the research uses of the model.

2014 ◽  
Vol 72 (6) ◽  
pp. 451-456 ◽  
Author(s):  
Eric Domingos Mariano ◽  
Chary Marquez Batista ◽  
Breno José Alencar Pires Barbosa ◽  
Suely Kazue Nagahashi Marie ◽  
Manoel Jacobsen Teixeira ◽  
...  

Spinal cord injury (SCI) and amyotrophic laterals sclerosis (ALS) are devastating neurological conditions that affect individuals worldwide, significantly reducing quality of life, both for patients and their relatives. Objective : The present review aims to summarize the multiple restorative approaches being developed for spinal cord repair, the use of different stem cell types and the current knowledge regarding stem cell therapy. Method : Review of the literature from the past 10 years of human studies using stem cell transplantation as the main therapy, with or without adjuvant therapies. Conclusion : The current review offers an overview of the state of the art regarding spinal cord restoration, and serves as a starting point for future studies.


Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2995
Author(s):  
Małgorzata Zawadzka ◽  
Anna Kwaśniewska ◽  
Krzysztof Miazga ◽  
Urszula Sławińska

Traumatic injury of the spinal cord (SCI) is a devastating neurological condition often leading to severe dysfunctions, therefore an improvement in clinical treatment for SCI patients is urgently needed. The potential benefits of transplantation of various cell types into the injured spinal cord have been intensively investigated in preclinical SCI models and clinical trials. Despite the many challenges that are still ahead, cell transplantation alone or in combination with other factors, such as artificial matrices, seems to be the most promising perspective. Here, we reviewed recent advances in cell-based experimental strategies supporting or restoring the function of the injured spinal cord with a particular focus on the regenerative mechanisms that could define their clinical translation.


2020 ◽  
Author(s):  
Simon Henmar ◽  
Erik B. Simonsen ◽  
Rune W. Berg

The gray matter of the spinal cord is the seat of somata of various types of neurons devoted to the sensory and motor activities of the limbs and trunk as well as a part of the autonomic nervous system. The volume of the spinal gray matter is an indicator of the local neuronal processing and this can decrease due to atrophy associated with degenerative diseases and injury. Nevertheless, the absolute volume of the human spinal cord has rarely been reported, if ever. Here, we use high–resolution magnetic resonance imaging, with a cross–sectional resolution of 50 × 50μm2 and a voxel size of 0.0005mm3, to estimate the total gray and white matter volume of a post mortem human female spinal cord. Segregation of gray and white matter was accomplished using deep learning image segmentation. Further, we include data from a male spinal cord of a previously published study. The gray and white matter volumes were found to be 2.87 and 11.33 ml, respectively for the female and 3.55 and 19.33 ml, respectively for a male. The gray and white matter profiles along the vertebral axis were found to be strikingly similar and the volumes of the cervical, thoracic and lumbosacral sections were almost equal.NEW AND NOTEWORTHYHere, we combine high field MRI (9.4T) and deep learning for a post-mortem reconstruction of the gray and white matter in human spinal cords. We report a minuscule total gray matter volume of 2.87 ml for a female and 3.55 ml for a male. For comparison, these volumes correspond approximately to the distal digit of the little finger.


Neurosurgery ◽  
1984 ◽  
Vol 15 (6) ◽  
pp. 893-899
Author(s):  
David Bowsher ◽  
Thoraya .E Abdel-Maguid

Abstract Golgi studies in the adult human spinal cord reveal 10 cell types in the first three laminae. Five are Golgi Type II or ipsilateral proprioneurons of short or long range-the latter including Waldeyer cells. Several of the cells in this group have dendrites that help to form interlaminar boundaries on the gray-white boundary. Two of the four cell types in Lamina II have dendritic fields that correspond exactly to the primary afferent terminal axonal fields described in the cat by Rethelyi (1977). Three cell types, one in each lamina, can be tentatively homologized with monkey spinothalamic cells described by other authors. Our previously described classification method based on dendritic patterns suggests that the Golgi Type II interneurons and ipsilateral proprioneurons belong to two different cell families (and Waldeyer cells to a third), whereas the putative spinothalamic neurons are all different cell types.


2021 ◽  
Author(s):  
Jimena Andersen ◽  
Nicholas Thom ◽  
Jennifer L Shadrach ◽  
Xiaoyu Chen ◽  
Neal D Amin ◽  
...  

Understanding spinal cord generation and assembly is essential to elucidate how motor behavior is controlled and how disorders arise. The cellular landscape of the human spinal cord remains, however, insufficiently explored. Here, we profiled the midgestation human spinal cord with single cell-resolution and discovered, even at this fetal stage, remarkable heterogeneity across and within cell types. Glia displayed diversity related to positional identity along the dorso-ventral and rostro-caudal axes, while astrocytes with specialized transcriptional programs mapped onto distinct histological domains. We discovered a surprisingly early diversification of alpha (α) and gamma (γ) motor neurons that control and modulate contraction of muscle fibers, which was suggestive of accelerated developmental timing in human spinal cord compared to rodents. Together with mapping of disease-related genes, this transcriptional profile of the developing human spinal cord opens new avenues for interrogating the cellular basis of motor control and related disorders in humans.


2018 ◽  
Vol 33 (1) ◽  
Author(s):  
Chuks Okpaluba

‘Accountability’ is one of the democratic values entrenched in the Constitution of South Africa, 1996. It is a value recognised throughout the Constitution and imposed upon the law-making organs of state, the Executive, the Judiciary and all public functionaries. This constitutional imperative is given pride of place among the other founding values: equality before the law, the rule of law and the supremacy of the Constitution. This study therefore sets out to investigate how the courts have grappled with the interpretation and application of the principle of accountability, the starting point being the relationship between accountability and judicial review. Therefore, in the exercise of its judicial review power, a court may enquire whether the failure of a public functionary to comply with a constitutional duty of accountability renders the decision made illegal, irrational or unreasonable. One of the many facets of the principle of accountability upon which this article dwells is to ascertain how the courts have deployed that expression in making the state and its agencies liable for the delictual wrongs committed against an individual in vindication of a breach of the individual’s constitutional right in the course of performing a public duty. Here, accountability and breach of public duty; the liability of the state for detaining illegal immigrants contrary to the prescripts of the law; the vicarious liability of the state for the criminal acts of the police and other law-enforcement officers (as in police rape cases and misuse of official firearms by police officers), and the liability of the state for delictual conduct in the context of public procurement are discussed. Having carefully analysed the available case law, this article concludes that no public functionary can brush aside the duty of accountability wherever it is imposed without being in breach of a vital constitutional mandate. Further, it is the constitutional duty of the courts, when called upon, to declare such act or conduct an infringement of the Constitution.


Author(s):  
Emma Puighermanal ◽  
Emmanuel Valjent

Addictive drugs trigger persistent synaptic and structural changes in the neuronal reward circuits that are thought to underlie the development of drug-adaptive behavior. While transcriptional and epigenetic modifications are known to contribute to these circuit changes, accumulating evidence indicates that altered mRNA translation is also a key molecular mechanism. This chapter reviews recent studies demonstrating how addictive drugs alter protein synthesis and/or the translational machinery and how this leads to neuronal circuit remodeling and behavioral changes. Future work will determine precisely which neuronal circuits and cell types participate in these changes. The chapter summarizes current methodologies for identifying cell type-specific mRNAs whose translation is affected by drugs of abuse and gives recent examples of the mechanistic insights into addiction they provide.


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