Inactivity-induced remodeling of neuromuscular junctions in rat diaphragmatic muscle

Prakash, Y. S.; Miyata, Hirofumi; Zhan, Wen Zhi; Sieck, Gary C.

doi:10.1002/(sici)1097-4598(199903)22:3<307::aid-mus3>3.0.co;2-m

Cited by 88 publications

(78 citation statements)

References 41 publications

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“…8,9,11,12,14,21 Briefly, the cervical spinal cord was exposed with a bilateral dorsal laminectomy at C2, and the right anterolateral cord was transected at C2 (i.e., involving the lateral and ventral funiculi, and preserving the dorsal funiculus). All animals were observed daily after surgery, and intramuscular buprenorphine and oral acetaminophen were administered for the first 3 days.…”

Section: Shmentioning

confidence: 99%

“…All SH animals displayed gross deficits related to the cervical spinal cord injury such as altered movements of the rib cage and abdomen consistent with hemidiaphragm paralysis. 8,9 Histological evidence of transplanted MSCs survival…”

Section: Intraspinal Injectionmentioning

confidence: 99%

“…5,6 SH involves a unilateral transection of anterolateral funiculi at C2, which removes premotor drive to phrenic motoneurons, paralyzing the ipsilateral diaphragm muscle. [7][8][9][10][11][12][13][14] Following SH, there is gradual recovery of rhythmic diaphragm activity ipsilateral to injury, [15][16][17][18][19][20][21] suggesting neuroplasticity and strengthening of spared contralateral synaptic inputs to phrenic motoneurons. Importantly, recovery of ipsilateral diaphragm activity after SH can be enhanced by intrathecal delivery of BDNF at the level of the phrenic motor nucleus.…”

Section: Introductionmentioning

confidence: 99%

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Localized Delivery of Brain-Derived Neurotrophic Factor-Expressing Mesenchymal Stem Cells Enhances Functional Recovery following Cervical Spinal Cord Injury

Gransee

Zhan

Sieck

et al. 2015

Journal of Neurotrauma

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113

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Neurotrophins, such as brain-derived neurotrophic factor (BDNF), are important in modulating neuroplasticity and promoting recovery after spinal cord injury. Intrathecal delivery of BDNF enhances functional recovery following unilateral spinal cord hemisection (SH) at C2, a well-established model of incomplete cervical spinal cord injury. We hypothesized that localized delivery of BDNF-expressing mesenchymal stem cells (BDNF-MSCs) would promote functional recovery of rhythmic diaphragm activity after SH. In adult rats, bilateral diaphragm electromyographic (EMG) activity was chronically monitored to determine evidence of complete SH at 3 days post-injury, and recovery of rhythmic ipsilateral diaphragm EMG activity over time post-SH. Wild-type, bone marrow-derived MSCs (WT-MSCs) or BDNF-MSCs (2 · 10 5 cells) were injected intraspinally at C2 at the time of injury. At 14 days post-SH, green fluorescent protein (GFP) immunoreactivity confirmed MSCs presence in the cervical spinal cord. Functional recovery in SH animals injected with WT-MSCs was not different from untreated SH controls (n = 10; overall, 20% at 7 days and 30% at 14 days). In contrast, functional recovery was observed in 29% and 100% of SH animals injected with BDNF-MSCs at 7 days and 14 days post-SH, respectively (n = 7). In BDNF-MSCs treated SH animals at 14 days, root-mean-squared EMG amplitude was 63 -16% of the pre-SH value compared with 12 -9% in the control/WT-MSCs group. We conclude that localized delivery of BDNF-expressing MSCs enhances functional recovery of diaphragm muscle activity following cervical spinal cord injury. MSCs can be used to facilitate localized delivery of trophic factors such as BDNF in order to promote neuroplasticity following spinal cord injury.

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Section: Shmentioning

confidence: 99%

Section: Intraspinal Injectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Localized Delivery of Brain-Derived Neurotrophic Factor-Expressing Mesenchymal Stem Cells Enhances Functional Recovery following Cervical Spinal Cord Injury

Gransee

Zhan

Sieck

et al. 2015

Journal of Neurotrauma

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113

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“…However, the CNTF null mice used in the present study (Masu et al, 1993) share the C57BL/6 background of the line used by Siegel et al, and display similar motor neuron deficits (Masu et al, 1993,DeChiara et al, 1995. The discrepancy is also unlikely to be attributable to variable sprouting competence among muscles examined in the two studies (Brown et al, 1980,Prakash et al, 1999,Pun et al, 2002,De Winter et al, 2006,Burns et al, 2007, because LAL, EDL and LG muscles are all fast-twitch muscles. Its response to paralysis also suggests that LAL is, like LG, a Delayed-synapsing muscle with robust sprouting capability (Pun et al, 2002).…”

Section: Discussionmentioning

confidence: 59%

Ciliary neurotrophic factor is not required for terminal sprouting and compensatory reinnervation of neuromuscular synapses: Re-evaluation of CNTF null mice

Wright

Son

2007

Experimental Neurology

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Loss of synaptic activity or innervation induces sprouting of intact motor nerve terminals that adds or restores nerve-muscle connectivity. Ciliary neurotrophic factor (CNTF) and terminal Schwann cells (tSCs) have been implicated as molecular and cellular mediators of the compensatory process. We wondered if the previously reported lack of terminal sprouting in CNTF null mice was due to abnormal reactivity of tSCs. To this end, we examined nerve terminal and tSC responses in CNTF null mice using experimental systems that elicited extensive sprouting in wildtype mice. Contrary to the previous report, we found that motor nerve terminals in the null mice sprout extensively in response to major sprouting-stimuli such as exogenously applied CNTF per se, botulinum toxinelicited paralysis, and partial denervation by L4 spinal root transection. In addition, the number, length and growth patterns of terminal sprouts, and the extent of reinnervation by terminal or nodal sprouts, were similar in wildtype and null mice. tSCs in the null mice were also reactive to the sprouting-stimuli, elaborating cellular processes that accompanied terminal sprouts or guided reinnervation of denervated muscle fibers. Lastly, CNTF was absent in quiescent tSCs in intact, wildtype muscles and little if any was detected in reactive tSCs in denervated muscles. Thus, CNTF is not required for induction of nerve terminal sprouting, for reactivation of tSCs, and for compensatory reinnervation after nerve injury. We interpret these results to support the notion that compensatory sprouting in adult muscles is induced primarily by contact-mediated mechanisms, rather than by diffusible factors.

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“…It has been clearly demonstrated that expression of these basal laminar proteins is altered by conditions that affect the integrity of the endplate and nerve terminal 18,19) . These results are in accordance with the recruitment patterns during normal respiration in the rat diaphragm muscle, in which only type I and type IIa motor units are recruited, and type IIx/b motor units are rarely recruited 20) .…”

Section: Motor Unit Organization and Recruitment Pattern Of The Diaphmentioning

confidence: 99%

Age and activity-related changes in the respiratory motor system

Miyata

2013

JPFSM

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The ability of the respiratory motor system to adapt to various functional demands is very important for maintaining human lifestyles. Age-related changes in the system have been studied in several animals. Furthermore, many kinds of models of altered use have been developed to examine activity-related changes in the system. In this review, the plasticity of the respiratory motor system, including spinal phrenic motoneurons and endplates on muscle fibers are discussed, mainly relating to inactivity and over-activity models in rat diaphragm muscle.

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Inactivity-induced remodeling of neuromuscular junctions in rat diaphragmatic muscle

Cited by 88 publications

References 41 publications

Localized Delivery of Brain-Derived Neurotrophic Factor-Expressing Mesenchymal Stem Cells Enhances Functional Recovery following Cervical Spinal Cord Injury

Localized Delivery of Brain-Derived Neurotrophic Factor-Expressing Mesenchymal Stem Cells Enhances Functional Recovery following Cervical Spinal Cord Injury

Ciliary neurotrophic factor is not required for terminal sprouting and compensatory reinnervation of neuromuscular synapses: Re-evaluation of CNTF null mice

Age and activity-related changes in the respiratory motor system

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