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  • 1
    In: Journal of Neurophysiology, American Physiological Society, Vol. 115, No. 3 ( 2016-03-01), p. 1372-1380
    Abstract: Power spectral analyses of electrical signals from respiratory nerves reveal prominent oscillations above the primary rate of breathing. Acute exposure to intermittent hypoxia can induce a form of neuroplasticity known as long-term facilitation (LTF), in which inspiratory burst amplitude is persistently elevated. Most evidence indicates that the mechanisms of LTF are postsynaptic and also that high-frequency oscillations within the power spectrum show coherence across different respiratory nerves. Since the most logical interpretation of this coherence is that a shared presynaptic mechanism is responsible, we hypothesized that high-frequency spectral content would be unchanged during LTF. Recordings of inspiratory hypoglossal (XII) activity were made from anesthetized, vagotomized, and ventilated 129/SVE mice. When arterial O 2 saturation (SaO 2 ) was maintained 〉 96%, the XII power spectrum and burst amplitude were unchanged for 90 min. Three, 1-min hypoxic episodes (SaO 2 = 50 ± 10%), however, caused a persistent ( 〉 60 min) and robust ( 〉 400% baseline) increase in burst amplitude. Spectral analyses revealed a rightward shift of the signal content during LTF, with sustained increases in content above ∼125 Hz following intermittent hypoxia and reductions in power at lower frequencies. Changes in the spectral content during LTF were qualitatively similar to what occurred during the acute hypoxic response. We conclude that high-frequency content increases during XII LTF in this experimental preparation; this may indicate that intermittent hypoxia-induced plasticity in the premotor network contributes to expression of XII LTF.
    Type of Medium: Online Resource
    ISSN: 0022-3077 , 1522-1598
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    Language: English
    Publisher: American Physiological Society
    Publication Date: 2016
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  • 2
    In: Journal of Applied Physiology, American Physiological Society, Vol. 137, No. 1 ( 2024-07-01), p. 166-180
    Abstract: Respiratory deficits after C2 hemisection (C2Hx) have been well documented through single-sex investigations. Although ovarian sex hormones enable enhanced respiratory recovery observed in females 2 wk post-C2Hx, it remains unknown if sex impacts spontaneous respiratory recovery at chronic time points. We conducted a longitudinal study to provide a comprehensive sex-based characterization of respiratory neuromuscular recovery for 8 wk after C2Hx. We recorded ventilation and chronic diaphragm electromyography (EMG) output in awake, behaving animals, phrenic motor output in anesthetized animals, and performed diaphragm muscle histology in chronically injured male and female rodents. Our results show that females expressed a greater recovery of tidal volume and minute ventilation compared with males during subacute and chronic time points. Eupneic diaphragm EMG amplitude during wakefulness and phrenic motor amplitude are similar between sexes at all time points after injury. Our data also suggest that females have a greater reduction in ipsilateral diaphragm EMG amplitude during spontaneous deep breaths (e.g., sighs) compared with males. Finally, we show evidence for atrophy and remodeling of the fast, fatigable fibers ipsilateral to injury in females, but not in males. To our knowledge, the data presented here represent the first study to report sex-dependent differences in spontaneous respiratory recovery and diaphragm muscle morphology following chronic C2Hx. These data highlight the need to study both sexes to inform evidence-based therapeutic interventions in respiratory recovery after spinal cord injury (SCI). NEW & NOTEWORTHY In response to chronic C2 hemisection, female rodents display increased tidal volume during eupneic breathing compared with males. Females show a greater reduction in diaphragm electromyography (EMG) amplitude during spontaneous deep breaths (e.g., sighs) and atrophy and remodeling of fast, fatigable diaphragm fibers. Given that most rehabilitative interventions occur in the subacute to chronic stages of injury, these results highlight the importance of considering sex when developing and evaluating therapeutics after spinal cord injury.
    Type of Medium: Online Resource
    ISSN: 8750-7587 , 1522-1601
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    Language: English
    Publisher: American Physiological Society
    Publication Date: 2024
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  • 3
    Online Resource
    Online Resource
    Wiley ; 2020
    In:  Journal of Comparative Neurology Vol. 528, No. 9 ( 2020-06-15), p. 1535-1547
    In: Journal of Comparative Neurology, Wiley, Vol. 528, No. 9 ( 2020-06-15), p. 1535-1547
    Abstract: The spiny mouse ( Acomys cahirinus ) appears to be unique among mammals by showing little scarring or fibrosis after skin or muscle injury, but the Acomys response to spinal cord injury (SCI) is unknown. We tested the hypothesis that Acomys would have molecular and immunohistochemical evidence of reduced spinal inflammation and fibrosis following SCI as compared to C57BL/6 mice ( Mus ), which similar to all mammals studied to date exhibits spinal scarring following SCI. Initial experiments used two pathway‐focused RT‐PCR gene arrays (“wound healing” and “neurogenesis”) to evaluate tissue samples from the C2–C6 spinal cord 3 days after a C3/C4 hemi‐crush injury (C3Hc). Based on the gene array results, specific genes were selected for RT‐qPCR evaluation using species‐specific primers. The results supported our hypothesis by showing increased inflammation and fibrosis related gene expression ( Serpine 1 , Plau , and Timp1) in Mus as compared to Acomys ( p 〈  .05). RT‐qPCR also showed enhanced stem cell and axonal guidance related gene expression (Bmp2 , GDNF , and Shh) in Acomys compared to Mus ( p 〈  .05). Immunohistochemical evaluation of the spinal lesion at 4 weeks postinjury indicated less collagen IV immunostaining in Acomys ( p 〈  .05). Glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1(IBA1) immunostaining indicated morphological differences in the appearance of astrocytes and macrophages/microglia in Acomys . Collectively, the molecular and histologic results support the hypothesis that Acomys has reduced spinal inflammation and fibrosis following SCI. We suggest that Acomys may be a useful comparative model to study adaptive responses to SCI.
    Type of Medium: Online Resource
    ISSN: 0021-9967 , 1096-9861
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
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  • 4
    Online Resource
    Online Resource
    Elsevier BV ; 2018
    In:  Respiratory Physiology & Neurobiology Vol. 256 ( 2018-10), p. 4-14
    In: Respiratory Physiology & Neurobiology, Elsevier BV, Vol. 256 ( 2018-10), p. 4-14
    Type of Medium: Online Resource
    ISSN: 1569-9048
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
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  • 5
    In: The FASEB Journal, Wiley, Vol. 30, No. S1 ( 2016-04)
    Abstract: Retrograde transport of viral vectors following intramuscular injection allows for targeted gene delivery to motoneuron pools. Gene delivery to the hypoglossal (XII) motoneurons is of potential interest in disorders involving impaired tongue muscle control such as dysphagia, dysarthria, and possibly obstructive sleep apnea. Using a murine model of Pompe disease, our group has shown that a single intramuscular injection of 1.00e11 vector genomes (vg) of recombinant adeno‐associated virus serotype 9 (AAV9) into the base of the tongue produces sustained transgene expression in a subset of XII motoneurons. Here we investigated whether distributing the virus over a broader portion of the tongue via two near‐simultaneous injections would increase XII motoneuron transduction as compared to a single injection. Four week old 129SVE mice were anesthetized and administered either a unilateral, single 20μL injection (n=2) or bilateral, 10μL injections (n=2) to the anterior base of the tongue targeting the insertion point for the genioglossus muscle. In both cases, a total of 1.00e11 vg of AAV9 encoding green fluorescent protein (GFP) with expression driven by the chicken β‐actin promotor (AAV9‐CBA‐GFP) was given. The medulla was histologically evaluated 6 weeks after tongue injection; GFP was detected using immunohistochemistry. Robust XII motoneuron GFP expression was observed in the caudal XII nucleus after either single or dual AAV9 injection; initial observations suggest no differences in XII motoneuron transduction between the two delivery methods. With both approaches, GFP expression was primarily restricted to XII motoneurons, but was also sporadically present in neurons throughout the medulla. The data confirm that tongue injection of AAV9 drives robust transgene expression in the XII motoneuron pool, and suggest that expression is similar whether using the single or dual injection approach. Support or Funding Information 2R01HD052682‐06A1
    Type of Medium: Online Resource
    ISSN: 0892-6638 , 1530-6860
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2016
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  • 6
    Online Resource
    Online Resource
    Wiley ; 2022
    In:  The FASEB Journal Vol. 36, No. S1 ( 2022-05)
    In: The FASEB Journal, Wiley, Vol. 36, No. S1 ( 2022-05)
    Abstract: Activation of phrenic afferents increases phrenic motor output and induces short‐term plasticity. Here we tested the hypothesis that activation of phrenic afferents via acute diaphragm stimulation induces neuromuscular plasticity within the phrenic motor system. Bilateral EMG activity was recorded from the mid‐costal diaphragm of anesthetized and spontaneously breathing rats. Inspiratory‐triggered stimulation was delivered to the left diaphragm for 30 minutes at twitch threshold (n=7; 0.6 ± 0 mA) or 1.5X twitch threshold (n=7; 1.0 ± 0.12 mA), and output was recorded for 60 minutes post‐stimulation. Arterial blood gas samples revealed that PaCO 2 was no different than baseline during or after stimulation (P=0.2204) or across experimental groups (P=0.3534). Diaphragm amplitude ipsilateral and contralateral to stimulation was increased 60 minutes following threshold (P=0.0021 and P=0.0096) and 1.5X threshold (P=0.0003 and P=0.0448) stimulation compared to time controls (n=7). Separate groups of rats received 1.5X threshold stimulation and either a C3‐C6 laminectomy (n=6; 0.8 ± 0.06mA) or a left C3‐C6 dorsal rhizotomy (n=6; 0.7 ± 0.10mA) to prevent afferent input from reaching the spinal cord. Laminectomy controls continued to express neuromuscular plasticity ipsilateral (P=0.0017) and contralateral (P=0.0076) to stimulation compared to time controls. By contrast, following unilateral dorsal rhizotomy, ipsilateral and contralateral diaphragm amplitude 60 minutes post‐stimulation was lower than laminectomy controls (P=0.0107 and P=0.0115) and no different than time controls (P=0.5692 and P=0.4784), suggesting neuromuscular plasticity was not induced. Our results indicate that acute diaphragm stimulation induces a novel form of neuromuscular plasticity which requires activation of phrenic afferents. We hypothesize that phrenic afferent induced neuromuscular plasticity may be valuable as a therapeutic strategy following spinal cord injury.
    Type of Medium: Online Resource
    ISSN: 0892-6638 , 1530-6860
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
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  • 7
    In: The FASEB Journal, Wiley, Vol. 33, No. S1 ( 2019-04)
    Abstract: Anatomical data from our laboratory indicate that phrenic afferent fibers can project across the spinal midline and neurophysiological data indicate that electrical activation of phrenic afferents can increase contralateral phrenic motor output. We have also observed that following chronic unilateral C2 hemisection (C2Hx) phrenic nerve afferent fibers undergo significant anatomical remodeling. Here we tested the hypothesis that following chronic C2Hx, activation of ipsilateral (same side as injury) phrenic afferent neurons would induce contralateral (opposite to injury) phrenic motor plasticity. Twelve weeks after unilateral C2Hx (n=9) or C2 laminectomy (n=8), adult Sprague‐Dawley rats were anesthetized, vagotomized, and ventilated to enable phrenic motor output to be studied under controlled conditions. The phrenic nerve ipsilateral to C2Hx or laminectomy was electrically stimulated using a bipolar electrode while contralateral phrenic motor output was recorded. Rats received 30 minutes of inspiratory triggered stimulation (90μA, 40pps, 1ms pulse width) and contralateral phrenic motor output was recorded for one hour. Analysis of contralateral burst amplitude using a two‐way repeated measures ANOVA revealed a significant effect of time (F 3,45 =9.505, P 〈 0.0001), but not treatment (C2Hx vs. laminectomy, F 1,15 =0.1577, P=0.6969). Thus, phrenic burst amplitude was significantly changing over the 60 minute post‐stimulation, and both experimental groups had increased phrenic burst amplitude during this period (P 〈 0.05 vs. pre‐stimulation baseline). These results indicate that electrical activation of phrenic nerve afferent fibers can induce a sustained increased (facilitation) of contralateral phrenic motor output after spinal cord injury. The response was not statistically different in the laminectomy group, which indicates that the phrenic afferent‐induced facilitation does not require conditions induced by the spinal cord injury. The ability of phrenic afferent neurons to evoke phrenic motor plasticity after spinal cord injury suggests that these afferent pathways could be important to rehabilitation of the diaphragm motor system post‐injury. Support or Funding Information K99HL143207‐01 (KS), F32NS095620‐01 (KS), T32HL134621‐01A1 (LBW), SPARC OT2 OD023854 (DDF) This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
    Type of Medium: Online Resource
    ISSN: 0892-6638 , 1530-6860
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2019
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  • 8
    Online Resource
    Online Resource
    American Physiological Society ; 2021
    In:  Journal of Neurophysiology Vol. 126, No. 6 ( 2021-12-01), p. 2091-2103
    In: Journal of Neurophysiology, American Physiological Society, Vol. 126, No. 6 ( 2021-12-01), p. 2091-2103
    Abstract: Phrenic afferents project to brainstem areas responsible for cardiorespiratory control and the mid-cervical spinal cord containing the phrenic motor nucleus. Our purpose was to quantify the impact of small- and large-diameter phrenic afferent activation on phrenic motor output. Anesthetized and ventilated rats received unilateral phrenic nerve stimulation while contralateral phrenic motor output and blood pressure were recorded. Twelve currents of 40-Hz inspiratory-triggered stimulation were delivered (20 s on, 5 min off) to establish current response curves. Stimulation pulse width was varied to preferentially activate large-diameter phrenic afferents (narrow pulse width) and recruit small-diameter fibers (wide pulse width). Contralateral phrenic amplitude was elevated immediately poststimulation at currents above 35 µA for wide and 70 µA for narrow pulse stimulation when compared with animals not receiving stimulation (time controls). Wide pulse width stimulation also increased phrenic burst frequency at currents ≥35 µA, caused a transient decrease in mean arterial blood pressure at currents ≥50 µA, and resulted in a small change in heart rate at 300 µA. Unilateral dorsal rhizotomy attenuated stimulation-induced cardiorespiratory responses indicating that phrenic afferent activation is required. Additional analyses compared phrenic motor amplitude with output before stimulation and showed that episodic activation of phrenic afferents with narrow pulse stimulation can induce short-term plasticity. We conclude that the activation of phrenic afferents 1) enhances contralateral phrenic motor amplitude when large-diameter afferents are activated, and 2) when small-diameter fibers are recruited, the amplitude response is associated with changes in burst frequency and cardiovascular parameters. NEW & NOTEWORTHY Acute, inspiratory-triggered stimulation of phrenic afferents increases contralateral phrenic motor amplitude in adult rats. When small-diameter afferents are recruited, the amplitude response is accompanied by an increase in phrenic burst frequency, a transient decrease in mean arterial blood pressure, and a slight increase in heart rate. Repeated episodes of large-diameter phrenic afferent activation may also be capable of inducing short-term plasticity.
    Type of Medium: Online Resource
    ISSN: 0022-3077 , 1522-1598
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    Language: English
    Publisher: American Physiological Society
    Publication Date: 2021
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    detail.hit.zdb_id: 1467889-5
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  • 9
    Online Resource
    Online Resource
    Wiley ; 2020
    In:  Journal of Comparative Neurology Vol. 528, No. 9 ( 2020-06-15)
    In: Journal of Comparative Neurology, Wiley, Vol. 528, No. 9 ( 2020-06-15)
    Type of Medium: Online Resource
    ISSN: 0021-9967 , 1096-9861
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 3086-7
    detail.hit.zdb_id: 1474879-4
    SSG: 12
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  • 10
    Online Resource
    Online Resource
    Society for Neuroscience ; 2017
    In:  The Journal of Neuroscience Vol. 37, No. 35 ( 2017-08-30), p. 8349-8362
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 37, No. 35 ( 2017-08-30), p. 8349-8362
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2017
    detail.hit.zdb_id: 1475274-8
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    SSG: 12
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