Caudal optogenetic spinal stimulation promotes better therapeutic outcomes than rostral optogenetic…

Abstract

Purpose: Spinal stimulation, including optogenetic stimulation, is a promising therapeutic approach for promoting functional recovery after spinal cord injury (SCI). To date, most studies have delivered stimulation caudal to the level of the lesion. Therefore, there is a lack of understanding of how spinal stimulation rostral to the lesion may affect recovery. Here, we investigate the effects of optogenetic spinal stimulation rostral to the lesion site on forelimb functional recovery and axonal growth in a rat model of cervical SCI.

Methods: Female Long-Evans rats received a C4 hemicontusion, intraspinal injections of an optogenetic viral vector rostral to the injury site, and a micro-light-emitting diode (μLED) implant for optogenetic stimulation. Beginning 6 weeks post-injury, rats received 6 weeks of optogenetic or sham stimulation alongside forelimb reaching rehabilitation. Forelimb reaching success and growth-associated protein 43 (GAP43) percent area were compared with those in our previous study, which evaluated an identical paradigm, but with optogenetic stimulation positioned caudal to the injury.

Results: The present results indicate that rostral stimulation did not enhance forelimb recovery on the forelimb reaching task and that forelimb reaching success was significantly higher in the caudal optogenetic stimulation group compared to the rostral stimulation group. Additionally, rostral stimulation did not enhance axonal growth within the cervical spinal cord compared with sham stimulation, whereas caudal optogenetic stimulation promoted significantly more axonal growth than rostral optogenetic stimulation.

Conclusion: Overall, these results indicate that caudal optogenetic stimulation promotes a greater therapeutic impact than rostral optogenetic stimulation.

Viral Strategies for In Vivo Optogenetic Stimulation of Purkinje Cell Terminals and Electrophysiological Characterization of Downstream Cerebellar Nuclear Activity in Mice
E. Merino, S. J. Jung, E. G. Antzoulatos +1
bioRxiv27 Sep 2026PreprintAll rights reservedFull textNeurosciencebioRxiv
Comparable phosphene size and contrast properties, but differing detection reliability for optogenetic versus electrical stimulation of macaque V1
K. Liza, M. Falkowska-Kisiel, J. Cadena-Valencia +6
bioRxiv3 Sep 2026PreprintAll rights reservedFull textNeurosciencebioRxiv
Mice detect and discriminate temporal patterns of mesoscale optogenetic cortical stimulation
G. Stephens, N. Francis
bioRxiv17 Sep 2026PreprintCC BY-NC-NDFull textNeurosciencebioRxiv
Coordinated orienting behavior emerges following unilateral optogenetic activation of Superior Colliculus GABAergic neurons
H. Suyama, T. Lupashina, M. Hamon +6
bioRxiv27 Oct 2026PreprintCC BYFull textNeurosciencebioRxiv
Optogenetic modeling of wake-like transcriptional progression in human SH-SY5Y neuronal cells
Shintaro Yamazaki, William Gee, Utham K. Valekunja +1
Scientific Reports17 Oct 2026Peer-reviewedCC BY-NC-ND 4.0Full textNeuroscienceCrossref

Cite

BibTeX RIS

BibTeX

@article{myers2026caudal,
  title = {{Caudal optogenetic spinal stimulation promotes better therapeutic outcomes than rostral optogenetic stimulation following a cervical spinal cord injury}},
  author = {R. J. Myers and V. Dang and M. N. McGiffin and M. L. Trinh and S. E. Mondello},
  journal = {Frontiers in Neuroscience},
  year = {2026},
  month = oct,
  doi = {10.3389/fnins.2026.1939104},
  url = {https://www.frontiersin.org/articles/10.3389/fnins.2026.1939104/full},
  note = {CC BY 4.0},
}

RIS

TY  - JOUR
TI  - Caudal optogenetic spinal stimulation promotes better therapeutic outcomes than rostral optogenetic stimulation following a cervical spinal cord injury
AU  - R. J. Myers
AU  - V. Dang
AU  - M. N. McGiffin
AU  - M. L. Trinh
AU  - S. E. Mondello
PY  - 2026
DA  - 2026/10/20
JO  - Frontiers in Neuroscience
DO  - 10.3389/fnins.2026.1939104
UR  - https://www.frontiersin.org/articles/10.3389/fnins.2026.1939104/full
AB  - Purpose: Spinal stimulation, including optogenetic stimulation, is a promising therapeutic approach for promoting functional recovery after spinal cord injury (SCI). To date, most studies have delivered stimulation caudal to the level of the lesion. Therefore, there is a lack of understanding of how spinal stimulation rostral to the lesion may affect recovery. Here, we investigate the effects of optogenetic spinal stimulation rostral to the lesion site on forelimb functional recovery and axonal growth in a rat model of cervical SCI.  Methods: Female Long-Evans rats received a C4 hemicontusion, intraspinal injections of an optogenetic viral vector rostral to the injury site, and a micro-light-emitting diode (μLED) implant for optogenetic stimulation. Beginning 6 weeks post-injury, rats received 6 weeks of optogenetic or sham stimulation alongside forelimb reaching rehabilitation. Forelimb reaching success and growth-associated protein 43 (GAP43) percent area were compared with those in our previous study, which evaluated an identical paradigm, but with optogenetic stimulation positioned caudal to the injury.  Results: The present results indicate that rostral stimulation did not enhance forelimb recovery on the forelimb reaching task and that forelimb reaching success was significantly higher in the caudal optogenetic stimulation group compared to the rostral stimulation group. Additionally, rostral stimulation did not enhance axonal growth within the cervical spinal cord compared with sham stimulation, whereas caudal optogenetic stimulation promoted significantly more axonal growth than rostral optogenetic stimulation.  Conclusion: Overall, these results indicate that caudal optogenetic stimulation promotes a greater therapeutic impact than rostral optogenetic stimulation.
SN  - 1662-453X
SN  - 1662-4548
ER  -

Abstract

Related

Cite