Special Issue "Pathophysiology of Spinal Cord Injury (SCI)"

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Medical Biology".

Deadline for manuscript submissions: 31 January 2022.

Special Issue Editors

Dr. Cédric G. Geoffroy
E-Mail Website1 Website2
Guest Editor
Department of Neuroscience & Experimental Therapeutics, College of Medicine, Texas A&M Health Science Center, Bryan, TX 77807, USA
Interests: spinal cord injury; axon regeneration; aging; gene therapy; drug discovery; cardiometabolic disease; bowel dysfunction
Dr. Warren Alilain
E-Mail
Guest Editor
Spinal Cord and Brain Injury Research Center, Department of Neuroscience, University of Kentucky, College of Medicine, Lexington, KY 40536, USA
Interests: spinal cord injury; neural control of breathing; plasticity; axonal regeneration and sprouting; personalized medicine

Special Issue Information

Dear Colleagues,

Spinal cord injury (SCI) leads to paralysis, sensory, and autonomic nervous system dysfunctions. However, the pathophysiology of SCI is complex, not limited to the nervous system. Indeed, several other organs and tissue are also affected by the injury, directly or not, acutely or chronically, which induces numerous health complications. While a lot of research has been performed to repair motor and sensory functions, SCI-induced health issues are less studied, although they represent a major concern among patients. There is a gap of knowledge in pre-clinical models studying these SCI-induced health complications that limits translational applications in humans.

In this Special Issue of Biology, we encourage the submission of manuscripts on any aspects of the pathophysiology of spinal cord injuries. This includes, but is not limited to, the impact of SCI on cardiovascular function, bladder and bowel function, risk of infections associated with SCI, liver pathology, metabolic syndrome, bones and muscles loss, and cognitive functions. We welcome original research articles, review articles, and short communications. This Special Issue will provide an overview of the pre-clinical models available to study the pathophysiology of SCI, and bring experts in the field to discuss what is needed to increase the research and translational potential of SCI-induced health complications.

Dr. Cédric G. Geoffroy
Dr. Warren Alilain
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • spinal cord injury 
  • cardiovascular function 
  • bladder function 
  • bowel function 
  • infections 
  • liver pathology 
  • metabolic syndrome 
  • bone loss 
  • muscle loss 
  • cognitive functions 
  • sexual functions

Published Papers (5 papers)

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Research

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Article
Development of a Spinal Cord Injury Model Permissive to Study the Cardiovascular Effects of Rehabilitation Approaches Designed to Induce Neuroplasticity
Biology 2021, 10(10), 1006; https://doi.org/10.3390/biology10101006 - 07 Oct 2021
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Abstract
As primary medical care for spinal cord injury (SCI) has improved over the last decades there are more individuals living with neurologically incomplete (vs. complete) cervical injuries. For these individuals, a number of promising therapies are being actively researched in pre-clinical settings that [...] Read more.
As primary medical care for spinal cord injury (SCI) has improved over the last decades there are more individuals living with neurologically incomplete (vs. complete) cervical injuries. For these individuals, a number of promising therapies are being actively researched in pre-clinical settings that seek to strengthen the remaining spinal pathways with a view to improve motor function. To date, few, if any, of these interventions have been tested for their effectiveness to improve autonomic and cardiovascular (CV) function. As a first step to testing such therapies, we aimed to develop a model that has sufficient sparing of descending sympathetic pathways for these interventions to target yet induces robust CV impairment. Twenty-six Wistar rats were assigned to SCI (n = 13) or naïve (n = 13) groups. Animals were injured at the T3 spinal segment with 300 kdyn of force. Fourteen days post-SCI, left ventricular (LV) and arterial catheterization was performed to assess in vivo cardiac and hemodynamic function. Spinal cord lesion characteristics along with sparing in catecholaminergic and serotonergic projections were determined via immunohistochemistry. SCI produced a decrease in mean arterial pressure of 17 ± 3 mmHg (p < 0.001) and left ventricular contractility (end-systolic elastance) of 0.7 ± 0.1 mmHg/µL (p < 0.001). Our novel SCI model produced significant decreases in cardiac and hemodynamic function while preserving 33 ± 9% of white matter at the injury epicenter, which we believe makes it a useful pre-clinical model of SCI to study rehabilitation approaches designed to induce neuroplasticity. Full article
(This article belongs to the Special Issue Pathophysiology of Spinal Cord Injury (SCI))
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Article
What Makes a Successful Donor? Fecal Transplant from Anxious-Like Rats Does Not Prevent Spinal Cord Injury-Induced Dysbiosis
Biology 2021, 10(4), 254; https://doi.org/10.3390/biology10040254 - 24 Mar 2021
Cited by 2 | Viewed by 885
Abstract
Spinal cord injury (SCI) causes gut dysbiosis and an increased prevalence of depression and anxiety. Previous research showed a link between these two consequences of SCI by using a fecal transplant from healthy rats which prevented both SCI-induced microbiota changes and the subsequent [...] Read more.
Spinal cord injury (SCI) causes gut dysbiosis and an increased prevalence of depression and anxiety. Previous research showed a link between these two consequences of SCI by using a fecal transplant from healthy rats which prevented both SCI-induced microbiota changes and the subsequent development of anxiety-like behaviour. However, whether the physical and mental state of the donor are important factors in the efficacy of FMT therapy after SCI remains unknown. In the present study, rats received a fecal transplant following SCI from uninjured donors with increased baseline levels of anxiety-like behaviour and reduced proportion of Lactobacillus in their stool. This fecal transplant increased intestinal permeability, induced anxiety-like behaviour, and resulted in minor but long-term alterations in the inflammatory state of the recipients compared to vehicle controls. There was no significant effect of the fecal transplant on motor recovery in rehabilitative training, suggesting that anxiety-like behaviour did not affect the motivation to participate in rehabilitative therapy. The results of this study emphasize the importance of considering both the microbiota composition and the mental state of the donor for fecal transplants following spinal cord injury. Full article
(This article belongs to the Special Issue Pathophysiology of Spinal Cord Injury (SCI))
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Article
Delivery of the 5-HT2A Receptor Agonist, DOI, Enhances Activity of the Sphincter Muscle during the Micturition Reflex in Rats after Spinal Cord Injury
Biology 2021, 10(1), 68; https://doi.org/10.3390/biology10010068 - 19 Jan 2021
Viewed by 860
Abstract
Traumatic spinal cord injury (SCI) interrupts spinobulbospinal micturition reflex pathways and results in urinary dysfunction. Over time, an involuntary bladder reflex is established due to the reorganization of spinal circuitry. Previous studies show that manipulation of serotonin 2A (5-HT2A) receptors affects [...] Read more.
Traumatic spinal cord injury (SCI) interrupts spinobulbospinal micturition reflex pathways and results in urinary dysfunction. Over time, an involuntary bladder reflex is established due to the reorganization of spinal circuitry. Previous studies show that manipulation of serotonin 2A (5-HT2A) receptors affects recovered bladder function, but it remains unclear if this receptor regulates the activity of the external urethral sphincter (EUS) following SCI. To elucidate how central and peripheral serotonergic machinery acts on the lower urinary tract (LUT) system, we employed bladder cystometry and EUS electromyography recordings combined with intravenous or intrathecal pharmacological interventions of 5-HT2A receptors in female SCI rats. Three to four weeks after a T10 spinal transection, systemic and central blockage of 5-HT2A receptors with MDL only slightly influenced the micturition reflex. However, delivery of the 5-HT2A receptor agonist, DOI, increased EUS tonic activity and elicited bursting during voiding. Additionally, subcutaneous administration of DOI verified the enhancement of continence and voiding capability during spontaneous micturition in metabolic cage assays. Although spinal 5HT2A receptors may not be actively involved in the recovered micturition reflex, stimulating this receptor subtype enhances EUS function and the synergistic activity between the detrusor and sphincter to improve the micturition reflex in rats with SCI. Full article
(This article belongs to the Special Issue Pathophysiology of Spinal Cord Injury (SCI))
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Review

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Review
Plasticity in Cervical Motor Circuits following Spinal Cord Injury and Rehabilitation
Biology 2021, 10(10), 976; https://doi.org/10.3390/biology10100976 - 28 Sep 2021
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Abstract
Neuroplasticity is a robust mechanism by which the central nervous system attempts to adapt to a structural or chemical disruption of functional connections between neurons. Mechanical damage from spinal cord injury potentiates via neuroinflammation and can cause aberrant changes in neural circuitry known [...] Read more.
Neuroplasticity is a robust mechanism by which the central nervous system attempts to adapt to a structural or chemical disruption of functional connections between neurons. Mechanical damage from spinal cord injury potentiates via neuroinflammation and can cause aberrant changes in neural circuitry known as maladaptive plasticity. Together, these alterations greatly diminish function and quality of life. This review discusses contemporary efforts to harness neuroplasticity through rehabilitation and neuromodulation to restore function with a focus on motor recovery following cervical spinal cord injury. Background information on the general mechanisms of plasticity and long-term potentiation of the nervous system, most well studied in the learning and memory fields, will be reviewed. Spontaneous plasticity of the nervous system, both maladaptive and during natural recovery following spinal cord injury is outlined to provide a baseline from which rehabilitation builds. Previous research has focused on the impact of descending motor commands in driving spinal plasticity. However, this review focuses on the influence of physical therapy and primary afferent input and interneuron modulation in driving plasticity within the spinal cord. Finally, future directions into previously untargeted primary afferent populations are presented. Full article
(This article belongs to the Special Issue Pathophysiology of Spinal Cord Injury (SCI))
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Review
Peripheral Immune Dysfunction: A Problem of Central Importance after Spinal Cord Injury
Biology 2021, 10(9), 928; https://doi.org/10.3390/biology10090928 - 17 Sep 2021
Viewed by 843
Abstract
Individuals with spinal cord injuries (SCI) exhibit increased susceptibility to infection, with pneumonia consistently ranking as a leading cause of death. Despite this statistic, chronic inflammation and concurrent immune suppression have only recently begun to be explored mechanistically. Investigators have now identified numerous [...] Read more.
Individuals with spinal cord injuries (SCI) exhibit increased susceptibility to infection, with pneumonia consistently ranking as a leading cause of death. Despite this statistic, chronic inflammation and concurrent immune suppression have only recently begun to be explored mechanistically. Investigators have now identified numerous changes that occur in the peripheral immune system post-SCI, including splenic atrophy, reduced circulating lymphocytes, and impaired lymphocyte function. These effects stem from maladaptive changes in the spinal cord after injury, including plasticity within the spinal sympathetic reflex circuit that results in exaggerated sympathetic output in response to peripheral stimulation below injury level. Such pathological activity is particularly evident after a severe high-level injury above thoracic spinal cord segment 6, greatly increasing the risk of the development of sympathetic hyperreflexia and subsequent disrupted regulation of lymphoid organs. Encouragingly, studies have presented evidence for promising therapies, such as modulation of neuroimmune activity, to improve regulation of peripheral immune function. In this review, we summarize recent publications examining (1) how various immune functions and populations are affected, (2) mechanisms behind SCI-induced immune dysfunction, and (3) potential interventions to improve SCI individuals’ immunological function to strengthen resistance to potentially deadly infections. Full article
(This article belongs to the Special Issue Pathophysiology of Spinal Cord Injury (SCI))
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Monoaminergic Influence on Spinal Cord Injury: The Upside of Descending Spared Fibers
Authors: Gizelle N. K. Fauss and James W. Grau
Affiliation: Department of Psychological and Brain Sciences, Texas A&M University, College Station, TX, USA
Abstract: Spinal cord injury (SCI) often leads to the disruption of descending modulatory fibers. Indeed, secondary complications following the initial trauma such as inflammation, neuropathy and axotomy can lead to an exaggerated loss of descending regulation. Serotonin, dopamine and noradrenaline are common modulatory neurotransmitters that regulate various spinal functions through supraspinal systems. The loss of descending control over these processes after SCI can lead to hyperexcitability and central sensitization, the reduction of inhibitory regulation, and maladaptive plasticity. In fact, monoaminergic neuromodulators have been implicated in the propagation of neural damage, the development of allodynia and hyperalgesia, and the dysregulation of autonomic output. While extensive work has been conducted to determine the cellular mechanisms that underlie these modulators on neuropathic pain, locomotion, and autonomic function, little attention has been given to the body of literature that explore the impact of disrupted descending pathways on the maintenance of homeostatic processes such as neuroplasticity and cell survival in the context of SCI. This overview will focus on the consequences of monoaminergic dysregulation after SCI and how this influences cell loss, plasticity, and peripheral processes. We will consider the neuromodulatory fiber pathways that mediate these maladaptive effects and provide a discussion of potential therapeutic interventions that improve functional recovery.

Title: Osteopenia in a Mouse Model of Spinal Cord Injury: Effects of Age, Sex and Motor Function
Authors: Michelle Hook 1,*, Alyssa Falck 2, Ravali Dundumulla 1, Mabel Terminel 1, Cédric G. Geoffroy 1 and Dana Gaddy 2
Affiliation: 1 Neuroscience & Experimental Therapeutics, 8447 Riverside Pkwy, Bryan, TX 77807, USA
2 Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, 4458 TAMU, College Station, TX 77845, USA
Abstract: After spinal cord injury (SCI), 80% of individuals are diagnosed with osteopenia or osteoporosis. The dramatic loss of bone after SCI increases the potential for fractures 100-fold, with post-fracture complications occurring in 54% of cases. With the age of new SCI injuries increasing, we hypothesized that a SCI-induced reduction in weight bearing could further exacerbate age-induced bone loss. To test this, young (2-3 months) and old (20-30 months) male and female mice were given a moderate spinal contusion injury (T9-T10), and recovery was assessed for 28 days (BMS, rearing counts, distance traveled). Tibial trabecular bone volume was measured after 28 days with ex vivo microCT. While BMS scores did not differ across groups, older subjects travelled less in the open field and there was a decrease in rearing with age and SCI. Older subjects also had decreased bone volume, and SCI further reduced bone volume in females, with a trend in males. Interestingly, both rearing and total activity correlated with decreased bone volume. These data underscore the importance of load and use on bone mass. While partial weight-bearing does not stabilize/reverse bone loss in humans, our data suggest that therapies that simulate complete loading may be effective after SCI.
Keywords: spinal cord injury; osteopenia; bone loss; recovery of function

Title: The Effect of Chronic Spinal Cord Injury Severity on Cardiometabolic Function
Authors: Adel. B. Ghnenis 1, Calvin. L. Jones 1, Arthur Sefiani 1, and Cédric. G. Geoffroy *
Affiliation: Department of Neuroscience & Experimental Therapeutics, College of Medicine, Texas A&M Health Science Center, Bryan, TX 77807, USA
Abstract: Changes in cardiometabolic function contribute to morbidity and mortality after chronic spinal cord injury (SCI). We examined the effects of SCI severity overtime on cardiac and liver function, body composition, glucose metabolism, and functional recovery following moderate and severe thoracic SCI in mice. We observed significant structural and functional cardiac changes with increased prevalence of liver echogenicity and fibrosis in mice with severe SCI. Moreover, there were significant changes in body composition (fat and lean %) and functional recovery in response to SCI severity. We demonstrated that disturbances in cardiometabolic function following thoracic SCI vary significantly depending upon the severity of the injury.

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