Optical Stimulation for Restoration of Motor Function After Spinal Cord Injury

Mallory, Grant W.; Grahn, Peter J.; Hachmann, Jan T.; Luján, J. Luis; Lee, Kendall H.

doi:10.1016/j.mayocp.2014.12.004

Cited by 14 publications

(11 citation statements)

References 90 publications

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“…While many hurdles still remain, the transfection of peripheral nerves to enable optogenetic control of neuronal activity in humans is a distinct future possibility. 23,24 Our results demonstrate the potential of using epidural or intrathecal optic fibers for the optogentic control of specific sensory afferents as a therapeutic approach for the treatment of sensory disorders in humans.…”

Section: Discussionmentioning

confidence: 68%

Epidural optogenetics for controlled analgesia

et al. 2016

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BackgroundOptogenetic tools enable cell selective and temporally precise control of neuronal activity; yet, difficulties in delivering sufficient light to the spinal cord of freely behaving animals have hampered the use of spinal optogenetic approaches to produce analgesia. We describe an epidural optic fiber designed for chronic spinal optogenetics that enables the precise delivery of light at multiple wavelengths to the spinal cord dorsal horn and sensory afferents.ResultsThe epidural delivery of light enabled the optogenetic modulation of nociceptive processes at the spinal level. The acute and repeated activation of channelrhodopsin-2 expressing nociceptive afferents produced robust nocifensive behavior and mechanical sensitization in freely behaving mice, respectively. The optogenetic inhibition of GABAergic interneurons in the spinal cord dorsal horn through the activation of archaerhodopsin also produced a transient, but selective induction of mechanical hypersensitivity. Finally, we demonstrate the capacity of optogenetics to produce analgesia in freely behaving mice through the inhibition of nociceptive afferents via archaerhodopsin.ConclusionEpidural optogenetics provides a robust and powerful solution for activation of both excitatory and inhibitory opsins in sensory processing pathways. Our results demonstrate the potential of spinal optogenetics to modulate sensory behavior and produce analgesia in freely behaving animals.

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Section: Discussionmentioning

confidence: 68%

Epidural optogenetics for controlled analgesia

et al. 2016

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“…It has been shown that regulation of posttraumatic inflammation is required to improve functional recovery (13, 14), such as through depletion of macrophages (15) and delivery of anti-inflammatory chemicals to the spinal cord lesion site (16, 17). Therefore, SCI treatment strategies should not only focus on removal of injury factors but also need to suppress the excitotoxicity and the activation of macrophage/microglias (18–21).…”

Section: Introductionmentioning

confidence: 99%

Snx27 Deletion Promotes Recovery From Spinal Cord Injury by Neuroprotection and Reduces Macrophage/Microglia Proliferation

et al. 2018

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Sorting nexin 27 (SNX27) is an endosome-associated cargo adaptor that is involved in various pathologies and development of neurological diseases. However, the role of SNX27 in spinal cord injury (SCI) remains unclear. In this study, we found that SNX27 was up-regulated in injured mice spinal cords by western blot and immunofluorescence. A comparative analysis of Basso mouse scale (BMS), footprint test and corticospinal tract (CST) tracing in Snx27+/+ and Snx27+/− mice revealed that haploinsufficiency of SNX27 ameliorated the clinical symptoms of SCI. Based on the results of western blot and immunofluorescence, mechanistically, we found that SNX27 deficiency suppresses apoptotic caspase-3 induced neuronal death. In addition, SNX27 haploinsufficiency lowers the infiltration and activation of macrophage/microglia by suppressing their proliferation at the SCI lesion site. Together, these results suggest that down-regulation of SNX27 is a potential therapy targeting both acute neuronal death and chronic neuroinflammation, and promoting nerve repair after SCI.

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“…Loss of nociception can lead to significant health risks 66 , and given the critical roles that thermoreceptors and metaboreceptors play in exercise physiology 9 , 10 , they will be imperative for restoration of unsupervised function in the natural environment. Optically-based techniques for limb animation and control of muscles have already been demonstrated (review 67 ). Given the advantages of these methods over electrodes in terms of nerve damage, decreased muscle fatigue, and specificity, a natural extension of an optical interface for read-in is to combine with appropriate sensory information.…”

Section: Discussionmentioning

confidence: 99%

Imaging of electrical activity in small diameter fibers of the murine peripheral nerve with virally-delivered GCaMP6f

Anderson

Fontaine

Caldwell

et al. 2018

Sci Rep

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Current neural interfaces are hampered by lack of specificity and selectivity for neural interrogation. A method that might improve these interfaces is an optical peripheral nerve interface which communicates with individual axons via optogenetic reporters. To determine the feasibility of such an interface, we delivered the genetically encoded calcium indicator GCaMP6f to the mouse peripheral nerve by intramuscular injection of adenoassociated viral vector (AAV1) under the control of the CAG (chicken beta actin- cytomegalovirus hybrid promoter). Small diameter axons in the common peroneal nerve were transduced and demonstrated electrically inducible calcium transients ex vivo. Responses to single electrical stimuli were resolvable, and increasing the number of stimuli resulted in a monotonic increase in maximum fluorescence and a prolongation of calcium transient kinetics. This work demonstrates the viability of using a virally-delivered, genetically-encoded calcium indicator to read-out from peripheral nerve axons.

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Optical Stimulation for Restoration of Motor Function After Spinal Cord Injury

Cited by 14 publications

References 90 publications

Epidural optogenetics for controlled analgesia

Epidural optogenetics for controlled analgesia

Snx27 Deletion Promotes Recovery From Spinal Cord Injury by Neuroprotection and Reduces Macrophage/Microglia Proliferation

Imaging of electrical activity in small diameter fibers of the murine peripheral nerve with virally-delivered GCaMP6f

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