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Brain Sciences
Special Issues
Spinal Cord Injury
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Spinal Cord Injury

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Molecular and Cellular Neuroscience".

Deadline for manuscript submissions: closed (30 June 2025) | Viewed by 3878

Special Issue Editors

Prof. Dr. Mark H. Tuszynski

E-Mail Website
Guest Editor
Department of Neurosciences, University of California, San Diego, CA, USA
Interests: stem cells; gene therapy; spinal cord injury; Alzheimer’s disease; neurotrophic factors
Dr. Paul Lu

E-Mail Website
Guest Editor
Department of Neurosciences, University of California, San Diego, CA, USA
Interests: stem cells; spinal cord injury; neurotrophic factors

Special Issue Information

Dear Colleagues,

After more than a century of research into axonal regeneration after CNS injury, effective therapies promoting neural repair are still lacking. However, the field is making progress, and we are nearing this goal thanks to stem cells, neurotrophic factors, inhibitory extracellular matrix degradation, and clinical trials involving a variety of drug-based approaches for altering the intrinsic cellular state and excitability.

This Special Issue will address many of these approaches, alongside efforts to translate them to human clinical trials. It will also cover how the use of the best pre-clinical spinal cord injury models in a manner mimicking clinical trial protocols can enhance the probability of success, together with well-designed clinical trials. We hope that this Special Issue will be informative in relaying the state of the field.

Prof. Dr. Mark H. Tuszynski
Dr. Paul Lu
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 submissions that pass pre-check are 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. Brain Sciences 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 2200 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
  • axonal regeneration
  • neural stem cells
  • neural progenitor cells
  • synaptic connection
  • neuronal relay

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Published Papers (3 papers)

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Research

21 pages, 9850 KB  
Article
AAV2retro Enters Axons of Passage and Extensively Transduces Corticospinal Neurons After Injection into Spinal White Matter
by Kazuki T. Nakashima, Shanshan Wang and Michael J. Castle
Brain Sci. 2025, 15(10), 1058; https://doi.org/10.3390/brainsci15101058 - 28 Sep 2025
Viewed by 753
Abstract
Background: Adult neurons in the central nervous system often fail to regenerate after spinal cord injury (SCI). Regenerative gene therapies could potentially promote corticospinal axon regeneration, restoration of motor circuitry, and functional improvement after SCI, but translational methods for targeted gene delivery to [...] Read more.
Background: Adult neurons in the central nervous system often fail to regenerate after spinal cord injury (SCI). Regenerative gene therapies could potentially promote corticospinal axon regeneration, restoration of motor circuitry, and functional improvement after SCI, but translational methods for targeted gene delivery to corticospinal neurons are needed. AAV2retro is an engineered variant of the adeno-associated virus 2 (AAV2) capsid that demonstrates greatly enhanced retrograde transduction of projection neurons. When injected into spinal gray matter, AAV2retro retrogradely transduces neurons in the sensorimotor cortex that project to the injected spinal level. Methods: We initially hypothesized that injection of AAV2retro into the dorsal column white matter immediately rostral of a mouse cervical spinal injury would target transected axons and broadly transduce both forelimb and hindlimb corticospinal neurons. We tested this hypothesis by comparing four groups of mice treated with AAV2retro carrying the tdTomato reporter gene by (1) injection into intact C4 gray matter, (2) injection into intact C4 dorsal column white matter, (3) injection into C4 gray matter bordering a C5 dorsal column lesion, and (4) injection into C4 dorsal column white matter bordering a C5 dorsal column lesion. Results: After injection of AAV2retro into intact C4 dorsal column white matter, we observed extensive transduction of corticospinal neurons throughout both the forelimb and hindlimb sensorimotor cortical regions, and large numbers of transduced hindlimb corticospinal axons in the lumbar spinal cord. Dorsal column injections did not detectably damage the white matter beyond a narrow injection track. In contrast, after injection of intact C4 gray matter, we observed minimal labeling of neurons in the hindlimb sensorimotor cortex or corticospinal axons in the lumbar spinal cord. Conclusions: We conclude that AAV2retro can enter axons of passage in the dorsal column white matter of the spinal cord, and that injecting the cervical dorsal columns can efficiently target both forelimb and hindlimb corticospinal neurons in mice. This new approach for targeted gene delivery to corticospinal neurons could improve the safety and specificity of regenerative gene therapies for spinal cord injury. Full article
(This article belongs to the Special Issue Spinal Cord Injury)
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11 pages, 1656 KB  
Article
Spinal Cord Injury in Real Time: Intra-Operative Ultrasound for Acute Phase Examination in Non-Human Primates
by Eleni Sinopoulou, Michelle W. Chow, Numaira Obaid, Emily Chong, Yvette S. Nout-Lomas, Rachele Wurr, Ryan Macon, J. Russell Huie, Adam R. Ferguson, Mark H. Tuszynski, Michael S. Beattie, Jacqueline C. Bresnahan and Carolyn J. Sparrey
Brain Sci. 2025, 15(9), 1005; https://doi.org/10.3390/brainsci15091005 - 17 Sep 2025
Viewed by 612
Abstract
Background: A spinal cord contusion injury is among the most clinically relevant models for studying pathophysiology and for developing potential therapeutic interventions for spinal cord injuries (SCI). Methods: In this study, we implemented an intra-operative ultrasound (IOU) approach to precisely locate and examine [...] Read more.
Background: A spinal cord contusion injury is among the most clinically relevant models for studying pathophysiology and for developing potential therapeutic interventions for spinal cord injuries (SCI). Methods: In this study, we implemented an intra-operative ultrasound (IOU) approach to precisely locate and examine the lesion site at 5 and 10 min post-injury after a cervical hemi-contusion injury in a non-human primate (NHP) model. We assessed acute lesion progression from 5 to 10 min and then compared that to the lesion extent as measured by MRI 3 weeks later. Results: We observed a small increase in the rostrocaudal and mediolateral lesion area (mm2) from 5 to 10 min and a further 26% increase in the mediolateral lesion extent when comparing 5 and 10 min to 3 weeks post-injury. Conclusions: By enabling high-resolution ultrasound visualization of the hemicontusion lesion in vivo, this approach can provide critical insights into the early progression of SCI. It can help with further refining this preclinical SCI model and provide significant predictive value for the animals’ recovery post-injury. Full article
(This article belongs to the Special Issue Spinal Cord Injury)
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16 pages, 4307 KB  
Article
Conditioning Electrical Nerve Stimulation Enhances Functional Rewiring in a Mouse Model of Nerve Transfer to Treat Chronic Spinal Cord Injury
by Juan Sebastián Jara, Marwa A. Soliman, Amanda Bernstein, Paola di Grazia, Adam R. Ferguson, Justin M. Brown, Abel Torres-Espín and Edmund R. Hollis
Brain Sci. 2025, 15(3), 251; https://doi.org/10.3390/brainsci15030251 - 27 Feb 2025
Viewed by 1950
Abstract
Background/Objectives: Nerve transfer surgery is a state-of-the-art surgical approach to restore hand and arm function in individuals living with tetraplegia, significantly impacting daily life. While nearly a third of all individuals with chronic spinal cord injury may benefit from this intervention, variability in [...] Read more.
Background/Objectives: Nerve transfer surgery is a state-of-the-art surgical approach to restore hand and arm function in individuals living with tetraplegia, significantly impacting daily life. While nearly a third of all individuals with chronic spinal cord injury may benefit from this intervention, variability in outcomes can limit the functional impact. A bedside to bench approach was taken to address the variable response of tetraplegic individuals to nerve transfer surgery. Methods: We used a hierarchical multiple factor analysis to evaluate the effects of conditioning electrical stimulation (CES) on outcomes in a mouse model of nerve transfer to treat chronic cervical spinal cord injury. Results: We found that CES of donor nerves one week prior to nerve transfer surgery enhanced anatomical and functional measures of innervation of targeted muscles. Furthermore, CES increased the rate of recovery of naturalistic behavior. Conclusions: While the model has some limitations due to the small size of the rodent, our results support the use of CES as an effective approach to improve outcomes in clinical nerve repair settings. Full article
(This article belongs to the Special Issue Spinal Cord Injury)
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