Implantable and transcutaneous photobiomodulation promote neuroregeneration and recovery of lost function after spinal cord injury

Andrew R. Stevens, Mohammed Hadis, Alice Phillips, Abhinav Thareja, Michael Milward, Antonio Belli, William Palin, David J. Davies*, Zubair Ahmed*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

60 Downloads (Pure)

Abstract

Spinal cord injury (SCI) is a cause of profound and irreversible damage, with no effective therapy to promote functional recovery. Photobiomodulation (PBM) may provide a viable therapeutic approach using red or near-infrared light to promote recovery after SCI by mitigating neuroinflammation and preventing neuronal apoptosis. Our current study aimed to optimize PBM dose regimens and develop and validate the efficacy of an invasive PBM delivery paradigm for SCI. Dose optimization studies were performed using a serum withdrawal model of injury in cultures of primary adult rat dorsal root ganglion neurons (DRGN). Implantable and transcutaneous PBM delivery protocols were developed and validated using cadaveric modeling. The efficacy of PBM in promoting recovery after SCI in vivo was studied in a dorsal column crush injury model of SCI in adult rats. Optimal neuroprotection in vitro was achieved between 4 and 22 mW/cm2. 11 mW/cm2 for 1 min per day (0.66 J/cm2) increased cell viability by 45% over 5 days (p <0.0001), increasing neurite outgrowth by 25% (p < 0.01). A method for invasive application of PBM was developed using a diffusion-tipped optogenetics fiber optic. Delivery methods for PBM were developed and validated for both invasive (iPBM) and noninvasive (transcutaneous) (tcPBM) application. iPBM and tcPBM (24 mW/cm2 at spinal cord, 1 min per day (1.44 J/cm2) up to 7 days) increased activation of regeneration-associated protein at 3 days after SCI, increasing GAP43+ axons in DRGN from 18.0% (control) to 41.4% ± 10.5 (iPBM) and 45.8% ± 3.4 (tcPBM) (p < 0.05). This corresponded to significant improvements at 6 weeks post-injury in functional locomotor and sensory function recovery (p < 0.01), axonal regeneration (p < 0.01), and reduced lesion size (p < 0.01). Our results demonstrated that PBM achieved a significant therapeutic benefit after SCI, either using iPBM or tcPBM application and can potentially be developed for clinical use in SCI patients.
Original languageEnglish
JournalBioengineering & Translational Medicine
Early online date25 Apr 2024
DOIs
Publication statusE-pub ahead of print - 25 Apr 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.

Keywords

  • medical devices
  • spinal cord injury
  • spinal cord stimulation
  • neuroregeneration
  • photobiomodulation

ASJC Scopus subject areas

  • Biotechnology
  • Biomedical Engineering
  • Pharmaceutical Science

Fingerprint

Dive into the research topics of 'Implantable and transcutaneous photobiomodulation promote neuroregeneration and recovery of lost function after spinal cord injury'. Together they form a unique fingerprint.

Cite this