VI. THE EFFECT UPON THE IPSILATERAL PERIPHERAL MOTOR NERVES OF STIMULATION OF THE EXTRAPYRAMIDAL SYSTEM

1953 ◽  
Vol 28 (S103) ◽  
pp. 41-48
2018 ◽  
Author(s):  
Jordan J. Williams ◽  
Alan M. Watson ◽  
Alberto L. Vazquez ◽  
Andrew B. Schwartz

AbstractObjectiveReanimation of muscles paralyzed by disease states such as spinal cord injury remains a much sought after therapeutic goal of neuroprosthetic research. Optogenetic stimulation of peripheral motor nerves expressing light-sensitive opsins is a promising approach to muscle reanimation that may overcome several drawbacks of traditional methods such as functional electrical stimulation (FES). However, the utility of these methods has only been demonstrated in rodents to date, while translation to clinical practice will likely first require demonstration and refinement of these gene therapy techniques in non-human primates.ApproachThree rhesus macaques were injected intramuscularly with either one or both of two optogenetic constructs (AAV6-hSyn-ChR2-eYFP and/or AAV6-hSyn-Chronos-eYFP) to transduce opsin expression in the corresponding nerves. Neuromuscular junctions were targeted for virus delivery using an electrical stimulating injection technique. Functional opsin expression was periodically evaluated up to 13 weeks post-injection by optically stimulating targeted nerves with a 472 nm fiber-coupled laser while recording electromyographic (EMG) responses.Main ResultsOne monkey demonstrated functional expression of ChR2 at 8 weeks post-injection in each of two injected muscles, while the second monkey briefly exhibited contractions coupled to optical stimulation in a muscle injected with the Chronos construct at 10 weeks. A third monkey injected only in one muscle with the ChR2 construct showed strong optically coupled contractions at 5 ½ weeks which then disappeared by 9 weeks. EMG responses to optical stimulation of ChR2-transduced nerves demonstrated graded recruitment relative to both stimulus pulse-width and light intensity, and were able to track stimulus trains up to 16 Hz. In addition, the EMG response to prolonged stimulation showed delayed fatigue over several minutes.SignificanceThese results demonstrate the feasibility of viral transduction of peripheral motor nerves for functional optical stimulation of motor activity in non-human primates, a variable timeline of opsin expression in a primate model closer to humans, and fundamental EMG response characteristics to optical nerve stimulation. Subsequently, they represent an important step in translating these optogenetic techniques as a clinically viable gene therapy.


2019 ◽  
Vol 13 ◽  
Author(s):  
Jordan J. Williams ◽  
Alan M. Watson ◽  
Alberto L. Vazquez ◽  
Andrew B. Schwartz

Development ◽  
1993 ◽  
Vol 119 (2) ◽  
pp. 533-543 ◽  
Author(s):  
K. Broadie ◽  
M. Bate

We have examined the role of innervation in directing embryonic myogenesis, using a mutant (prospero), which delays the pioneering of peripheral motor nerves of the Drosophila embryo. In the absence of motor nerves, myoblasts fuse normally to form syncytial myotubes, myotubes form normal attachments to the epidermis, and a larval musculature comparable to the wild-type pattern is generated and maintained. Likewise, the twist-expressing myoblasts that prefigure the adult musculature segregate normally in the absence of motor nerves, migrate to their final embryonic positions and continue to express twist until the end of embryonic development. In the absence of motor nerves, myotubes uncouple at the correct developmental stage to form single cells. Subsequently, uninnervated myotubes develop the mature electrical and contractile properties of larval muscles with a time course indistinguishable from normally innervated myotubes. We conclude that innervation plays no role in the patterning, morphogenesis, maintenance or physiological development of the somatic muscles in the Drosophila embryo.


2016 ◽  
Vol 16 (suppl 1) ◽  
pp. S83-S88 ◽  
Author(s):  
Ana Catarina Matos Ishigami Alvino ◽  
Luísa Rocha Medeiros de Mello ◽  
Jucille do Amaral Meneses Meira de Oliveira

Abstract Introduction: in 2015 an increasing number of congenital microcephaly cases were associated to maternal infection due to Zika virus. Some of these patients presented other alterations and arthrogryposis was the most frequently found. Arthrogryposis is defined as congenital joint contractures involving at least two different areas of the body. Description: arthrogryposis was found in 18 patients with congenital microcephaly due to Zika virus. 67% of the cases were vaginal deliveries. 50% of resuscitation performed in the delivery room was necessary. The mean birth weight was 2.371g, gestational age was 39 weeks and the head circumference was 28.3cm, 15 (83%) of these patients presented severe microcephaly. All the neonates resulted in concomitant hip joints and some also had knees, ankles and wrists affected. Nine neonates (50%) presented an early respiratory distress and four (22%) died due to respiratory failure. Discussion: the neurological result found in patients with Congenital Zika Syndrome seems to be associated to the maternal infection period. During the early stages of embryogenesis, in addition to microcephaly, could be related to the peripheral motor nerves leading to fetal akinesia, joint stiffness and arthrogryposis. These neonates tend to present greater morbimortality with the worst prognosis.


1987 ◽  
Vol 10 (8) ◽  
pp. 698-710 ◽  
Author(s):  
Robert G. Miller

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