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Reggie V Edgerton - One of the best experts on this subject based on the ideXlab platform.
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electrical neuromodulation of the cervical spinal cord facilitates forelimb skilled function recovery in spinal cord injured rats
Experimental Neurology, 2017Co-Authors: Monzurul Alam, Guillermo Garciaalias, Benita Jin, Jonathan Keyes, Hui Zhong, Roland R Roy, Yury Gerasimenko, Reggie V EdgertonAbstract:Enabling motor control by epidural electrical stimulation of the spinal cord is a promising therapeutic technique for the recovery of motor function after a spinal cord injury (SCI). Although epidural electrical stimulation has resulted in improvement in hindlimb motor function, it is unknown whether it has any therapeutic benefit for improving forelimb fine motor function after a cervical SCI. We tested whether trains of pulses delivered at spinal cord segments C6 and C8 would facilitate the recovery of forelimb fine motor control after a cervical SCI in rats. Rats were trained to reach and grasp sugar pellets. Immediately after a dorsal funiculus crush at C4, the rats showed significant deficits in forelimb fine motor control. The rats were tested to reach and grasp with and without cervical epidural stimulation for 10weeks post-injury. To determine the best stimulation parameters to activate the cervical spinal networks involved in forelimb motor function, monopolar and bipolar currents were delivered at varying frequencies (20, 40, and 60Hz) concomitant with the reaching and grasping task. We found that cervical epidural stimulation increased reaching and grasping success rates compared to the no stimulation condition. Bipolar stimulation (C6- C8+ and C6+ C8-) produced the largest spinal motor-evoked potentials (sMEPs) and resulted in higher reaching and grasping success rates compared with monopolar stimulation (C6- Ref+ and C8- Ref+). Forelimb performance was similar when tested at stimulation frequencies of 20, 40, and 60Hz. We also found that the EMG activity in most forelimb muscles as well as the co-activation between flexor and extensor muscles increased post-injury. With epidural stimulation, however, this trend was reversed indicating that cervical epidural spinal cord stimulation has therapeutic potential for rehabilitation after a cervical SCI.
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electrical neuromodulation of the cervical spinal cord facilitates forelimb skilled function recovery in spinal cord injured rats
Experimental Neurology, 2017Co-Authors: Monzurul Alam, Guillermo Garciaalias, Jonathan Keyes, Hui Zhong, Yury Gerasimenko, Daniel C Lu, Reggie V EdgertonAbstract:Abstract Enabling motor control by epidural electrical stimulation of the spinal cord is a promising therapeutic technique for the recovery of motor function after a spinal cord injury (SCI). Although epidural electrical stimulation has resulted in improvement in hindlimb motor function, it is unknown whether it has any therapeutic benefit for improving forelimb fine motor function after a cervical SCI. We tested whether trains of pulses delivered at spinal cord segments C6 and C8 would facilitate the recovery of forelimb fine motor control after a cervical SCI in rats. Rats were trained to reach and grasp sugar pellets. Immediately after a dorsal funiculus crush at C 4, the rats showed significant deficits in forelimb fine motor control. The rats were tested to reach and grasp with and without cervical epidural stimulation for 10 weeks post-injury. To determine the best stimulation parameters to activate the cervical spinal networks involved in forelimb motor function, monopolar and bipolar currents were delivered at varying frequencies (20, 40, and 60 Hz) concomitant with the reaching and grasping task. We found that cervical epidural stimulation increased reaching and grasping success rates compared to the no stimulation condition. Bipolar stimulation (C6– C8 + and C6 + C8–) produced the largest spinal motor-evoked potentials (sMEPs) and resulted in higher reaching and grasping success rates compared with monopolar stimulation (C6– Ref + and C8– Ref +). Forelimb performance was similar when tested at stimulation frequencies of 20, 40, and 60 Hz. We also found that the EMG activity in most forelimb muscles as well as the co-activation between flexor and extensor muscles increased post-injury. With epidural stimulation, however, this trend was reversed indicating that cervical epidural spinal cord stimulation has therapeutic potential for rehabilitation after a cervical SCI.
Eric D. Young - One of the best experts on this subject based on the ideXlab platform.
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2001) Proprioceptive information from the pinna provides somatosensory input to cat dorsal cochlear nucleus
2013Co-Authors: Patrick O Kanold, Eric D. YoungAbstract:The dorsal cochlear nucleus (DCN) is a second-order auditory structure that also receives nonauditory information, including somatosensory inputs from the dorsal column and spinal trigeminal nuclei. Here we investigate the peripheral sources of the somatosensory inputs to DCN. Electrical stimulation was applied to cervical nerves C1–C8, branches of C2, branches of the trigeminal nerve, and hindlimb nerves. The largest evoked potentials in the DCN were produced by C2 stimulation and by stimulation of its branches that innervate the pinna. Electrical stimulation of C2 produced a pattern of inhibition and excitation of DCN principal cells comparable with that seen in previous studies with stimulation of the primary somatosensory nuclei, suggesting that the same pathway was activated. Because C2 contains both proprioceptive and cutaneous fibers, we applied peripheral somatosensory stimulation to identify the effective somatosensory modalities. Only stimuli that activate pinna muscle receptors, such as stretch or vibration of the muscles connected to the pinna, were effective in driving DCN units, whereas cutaneous stimuli such as light touch, brushing of hairs, and stretching of skin were ineffective. These results suggest that the largest somatosensory inputs to the DCN originate from muscle receptors associated with the pinna. They support the hypothesis that a role of the DCN in hearing is to coordinate pinna orientation to sounds or to support correction for the effects of pinna orientation on sound-localization cues. Key words: auditory; somatosensory; dorsal cochlear nucleus; cat; pinna; multisensory; sound localization The output neurons of the dorsal cochlear nucleus (DCN) are sensitive to both auditory and somatosensory stimuli (Saadé et al., 1989; Young et al., 1995), suggesting a cross-modal associative role for the DCN. The somatosensory inputs to the DCN originate predominantly from the ipsilateral dorsal column and spinal trigeminal nuclei (abbreviated MSN for medullary somatosensor
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proprioceptive information from the pinna provides somatosensory input to cat dorsal cochlear nucleus
The Journal of Neuroscience, 2001Co-Authors: Patrick O Kanold, Eric D. YoungAbstract:The dorsal cochlear nucleus (DCN) is a second-order auditory structure that also receives nonauditory information, including somatosensory inputs from the dorsal column and spinal trigeminal nuclei. Here we investigate the peripheral sources of the somatosensory inputs to DCN. Electrical stimulation was applied to cervical nerves C1–C8, branches of C2, branches of the trigeminal nerve, and hindlimb nerves. The largest evoked potentials in the DCN were produced by C2 stimulation and by stimulation of its branches that innervate the pinna. Electrical stimulation of C2 produced a pattern of inhibition and excitation of DCN principal cells comparable with that seen in previous studies with stimulation of the primary somatosensory nuclei, suggesting that the same pathway was activated. Because C2 contains both proprioceptive and cutaneous fibers, we applied peripheral somatosensory stimulation to identify the effective somatosensory modalities. Only stimuli that activate pinna muscle receptors, such as stretch or vibration of the muscles connected to the pinna, were effective in driving DCN units, whereas cutaneous stimuli such as light touch, brushing of hairs, and stretching of skin were ineffective. These results suggest that the largest somatosensory inputs to the DCN originate from muscle receptors associated with the pinna. They support the hypothesis that a role of the DCN in hearing is to coordinate pinna orientation to sounds or to support correction for the effects of pinna orientation on sound-localization cues.
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Proprioceptive information from the pinna provides somatosensory input to cat dorsal cochlear nucleus
2001Co-Authors: Patrick O Kanold, Eric D. YoungAbstract:The dorsal cochlear nucleus (DCN) is a second-order auditory structure that also receives nonauditory information, including somatosensory inputs from the dorsal column and spinal tri-geminal nuclei. Here we investigate the peripheral sources of the somatosensory inputs to DCN. Electrical stimulation was applied to cervical nerves C1–C8, branches of C2, branches of the trigeminal nerve, and hindlimb nerves. The largest evoked potentials in the DCN were produced by C2 stimulation and by stimulation of its branches that innervate the pinna. Electrical stimulation of C2 produced a pattern of inhibition and excitation of DCN principal cells comparable with that seen in previous studies with stimulation of the primary somatosensory nuclei, suggesting that the same pathway was activated. Because C2 contains both proprioceptive and cutaneous fibers, we applied peripheral somatosensory stimulation to identify the effective somatosensory modalities. Only stimuli that activate pinna muscle receptors, such as stretch or vibration of the muscles connected to the pinna, were effective in driving DCN units, whereas cutaneous stimuli such as light touch, brushing of hairs, and stretching of skin were ineffective. These results suggest that the largest somatosensory inputs to the DCN originate from muscle receptors associated with the pinna. They support the hypothesis that a role of the DCN in hearing is to coordinate pinna orientation to sounds or to support correc-tion for the effects of pinna orientation on sound-localization cues. Key words: auditory; somatosensory; dorsal cochlear nu-cleus; cat; pinna; multisensory; sound localization The output neurons of the dorsal cochlear nucleus (DCN) are sensitive to both auditory and somatosensory stimuli (Saade ́ et al., 1989; Young et al., 1995), suggesting a cross-modal associative role for the DCN. The somatosensory inputs to the DCN origi-nate predominantly from the ipsilateral dorsal column and spinal trigeminal nuclei (abbreviated MSN for medullary somatosensor
Kraan, P.m. Van Der - One of the best experts on this subject based on the ideXlab platform.
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Interleukin 1 beta-induced SMAD2/3 linker modifications are TAK1 dependent and delay TGFbeta signaling in primary human mesenchymal stem cells
'Elsevier BV', 2017Co-Authors: Akker, G.g.h. Van Den, Beuningen, H.m. Van, Vitters E.l., Koenders M.i., Loo, F.a.j. Van De, Lent, P.l.e.m. Van, Davidson E.n., Kraan, P.m. Van DerAbstract:Contains fulltext : 181933.pdf (publisher's version ) (Closed access)BACKGROUND: Chondrogenic differentiation of mesenchymal stem cells (MSC) requires transforming growth factor beta (TGFbeta) signaling. TGFbeta binds to the type I receptor activin-like kinase (ALK)5 and results in C-terminal SMAD2/3 phosphorylation (pSMAD2/3C). In turn pSMAD2/3C translocates to the nucleus and regulates target gene expression. Inflammatory mediators are known to exert an inhibitory effect on MSC differentiation. In this study we investigated the effect of interleukin 1 beta (IL1beta) on SMAD2/3 signaling dynamics and post-translational modifications. RESULTS: Co-Stimulation of MSC with TGFbeta and IL1beta did not affect peak pSMAD2C levels at 1h post-stimulation. Surprisingly, SMAD3 transcriptional activity, as determined by the CAGA12-luciferase reporter construct, was enhanced by Co-Stimulation of TGFbeta and IL1beta compared to TGFbeta alone. Furthermore, IL1beta stimulation induced CAGA12-luciferase activity in a SMAD dependent way. As SMAD function can be modulated independent of canonical TGFbeta signaling through the SMAD linker domain, we studied SMAD2 linker phosphorylation at specific threonine and serine residues. SMAD2 linker threonine and serine modifications were observed within 1h following TGFbeta, IL1beta or TGFbeta and IL1beta stimulation. Upon Co-Stimulation linker modified SMAD2 accumulated in the cytoplasm and SMAD2/3 target gene transcription (ID1, JUNB) at 2-4h was inhibited. A detailed time course analysis of IL1beta-induced SMAD2 linker modifications revealed a distinct temperospatial pattern compared to TGFbeta. Co-Stimulation with both factors resulted in a similar kinetic profile as TGFbeta alone. Nevertheless, IL1beta did subtly alter TGFbeta-induced pSMAD2C levels between 8 and 24h post-stimulation, which was reflected by TGFbeta target gene expression (PAI1, JUNB). Direct evidence for the importance of SMAD3 linker modifications for the effect of IL1beta on TGFbeta signaling was obtained by over-expression of SMAD3 or a SMAD3 linker phospho-mutant. Finally, an inhibitor screening was performed to identify kinases involved in SMAD2/3 linker modifications. We identified TAK1 kinase activity as crucial for IL1beta-induced SMAD2 linker modifications and CAGA12-luciferase activity. CONCLUSIONS: TGFbeta and IL1beta signaling interact at the SMAD2/3 level in human primary MSC. Down-stream TGFbeta target genes were repressed by IL1beta independent of C-terminal SMAD2 phosphorylation. We demonstrate that SMAD2/3 linker modifications are required for this interplay and identified TAK1 as a crucial mediator of IL1beta-induced TGFbeta signal modulation
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Interleukin 1 beta-induced SMAD2/3 linker modifications are TAK1 dependent and delay TGFbeta signaling in primary human mesenchymal stem cells
2017Co-Authors: Akker, G.g.h. Van Den, Beuningen, H.m. Van, Vitters E.l., Koenders M.i., Loo, F.a.j. Van De, Lent, P.l.e.m. Van, Davidson E.n., Kraan, P.m. Van DerAbstract:BACKGROUND: Chondrogenic differentiation of mesenchymal stem cells (MSC) requires transforming growth factor beta (TGFbeta) signaling. TGFbeta binds to the type I receptor activin-like kinase (ALK)5 and results in C-terminal SMAD2/3 phosphorylation (pSMAD2/3C). In turn pSMAD2/3C translocates to the nucleus and regulates target gene expression. Inflammatory mediators are known to exert an inhibitory effect on MSC differentiation. In this study we investigated the effect of interleukin 1 beta (IL1beta) on SMAD2/3 signaling dynamics and post-translational modifications. RESULTS: Co-Stimulation of MSC with TGFbeta and IL1beta did not affect peak pSMAD2C levels at 1h post-stimulation. Surprisingly, SMAD3 transcriptional activity, as determined by the CAGA12-luciferase reporter construct, was enhanced by Co-Stimulation of TGFbeta and IL1beta compared to TGFbeta alone. Furthermore, IL1beta stimulation induced CAGA12-luciferase activity in a SMAD dependent way. As SMAD function can be modulated independent of canonical TGFbeta signaling through the SMAD linker domain, we studied SMAD2 linker phosphorylation at specific threonine and serine residues. SMAD2 linker threonine and serine modifications were observed within 1h following TGFbeta, IL1beta or TGFbeta and IL1beta stimulation. Upon Co-Stimulation linker modified SMAD2 accumulated in the cytoplasm and SMAD2/3 target gene transcription (ID1, JUNB) at 2-4h was inhibited. A detailed time course analysis of IL1beta-induced SMAD2 linker modifications revealed a distinct temperospatial pattern compared to TGFbeta. Co-Stimulation with both factors resulted in a similar kinetic profile as TGFbeta alone. Nevertheless, IL1beta did subtly alter TGFbeta-induced pSMAD2C levels between 8 and 24h post-stimulation, which was reflected by TGFbeta target gene expression (PAI1, JUNB). Direct evidence for the importance of SMAD3 linker modifications for the effect of IL1beta on TGFbeta signaling was obtained by over-expression of SMAD3 or a SMAD3 linker phospho-mutant. Finally, an inhibitor screening was performed to identify kinases involved in SMAD2/3 linker modifications. We identified TAK1 kinase activity as crucial for IL1beta-induced SMAD2 linker modifications and CAGA12-luciferase activity. CONCLUSIONS: TGFbeta and IL1beta signaling interact at the SMAD2/3 level in human primary MSC. Down-stream TGFbeta target genes were repressed by IL1beta independent of C-terminal SMAD2 phosphorylation. We demonstrate that SMAD2/3 linker modifications are required for this interplay and identified TAK1 as a crucial mediator of IL1beta-induced TGFbeta signal modulation
Monzurul Alam - One of the best experts on this subject based on the ideXlab platform.
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electrical neuromodulation of the cervical spinal cord facilitates forelimb skilled function recovery in spinal cord injured rats
Experimental Neurology, 2017Co-Authors: Monzurul Alam, Guillermo Garciaalias, Benita Jin, Jonathan Keyes, Hui Zhong, Roland R Roy, Yury Gerasimenko, Reggie V EdgertonAbstract:Enabling motor control by epidural electrical stimulation of the spinal cord is a promising therapeutic technique for the recovery of motor function after a spinal cord injury (SCI). Although epidural electrical stimulation has resulted in improvement in hindlimb motor function, it is unknown whether it has any therapeutic benefit for improving forelimb fine motor function after a cervical SCI. We tested whether trains of pulses delivered at spinal cord segments C6 and C8 would facilitate the recovery of forelimb fine motor control after a cervical SCI in rats. Rats were trained to reach and grasp sugar pellets. Immediately after a dorsal funiculus crush at C4, the rats showed significant deficits in forelimb fine motor control. The rats were tested to reach and grasp with and without cervical epidural stimulation for 10weeks post-injury. To determine the best stimulation parameters to activate the cervical spinal networks involved in forelimb motor function, monopolar and bipolar currents were delivered at varying frequencies (20, 40, and 60Hz) concomitant with the reaching and grasping task. We found that cervical epidural stimulation increased reaching and grasping success rates compared to the no stimulation condition. Bipolar stimulation (C6- C8+ and C6+ C8-) produced the largest spinal motor-evoked potentials (sMEPs) and resulted in higher reaching and grasping success rates compared with monopolar stimulation (C6- Ref+ and C8- Ref+). Forelimb performance was similar when tested at stimulation frequencies of 20, 40, and 60Hz. We also found that the EMG activity in most forelimb muscles as well as the co-activation between flexor and extensor muscles increased post-injury. With epidural stimulation, however, this trend was reversed indicating that cervical epidural spinal cord stimulation has therapeutic potential for rehabilitation after a cervical SCI.
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electrical neuromodulation of the cervical spinal cord facilitates forelimb skilled function recovery in spinal cord injured rats
Experimental Neurology, 2017Co-Authors: Monzurul Alam, Guillermo Garciaalias, Jonathan Keyes, Hui Zhong, Yury Gerasimenko, Daniel C Lu, Reggie V EdgertonAbstract:Abstract Enabling motor control by epidural electrical stimulation of the spinal cord is a promising therapeutic technique for the recovery of motor function after a spinal cord injury (SCI). Although epidural electrical stimulation has resulted in improvement in hindlimb motor function, it is unknown whether it has any therapeutic benefit for improving forelimb fine motor function after a cervical SCI. We tested whether trains of pulses delivered at spinal cord segments C6 and C8 would facilitate the recovery of forelimb fine motor control after a cervical SCI in rats. Rats were trained to reach and grasp sugar pellets. Immediately after a dorsal funiculus crush at C 4, the rats showed significant deficits in forelimb fine motor control. The rats were tested to reach and grasp with and without cervical epidural stimulation for 10 weeks post-injury. To determine the best stimulation parameters to activate the cervical spinal networks involved in forelimb motor function, monopolar and bipolar currents were delivered at varying frequencies (20, 40, and 60 Hz) concomitant with the reaching and grasping task. We found that cervical epidural stimulation increased reaching and grasping success rates compared to the no stimulation condition. Bipolar stimulation (C6– C8 + and C6 + C8–) produced the largest spinal motor-evoked potentials (sMEPs) and resulted in higher reaching and grasping success rates compared with monopolar stimulation (C6– Ref + and C8– Ref +). Forelimb performance was similar when tested at stimulation frequencies of 20, 40, and 60 Hz. We also found that the EMG activity in most forelimb muscles as well as the co-activation between flexor and extensor muscles increased post-injury. With epidural stimulation, however, this trend was reversed indicating that cervical epidural spinal cord stimulation has therapeutic potential for rehabilitation after a cervical SCI.
Krisztina L Malisza - One of the best experts on this subject based on the ideXlab platform.
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functional mri of the cervical spinal cord during noxious and innocuous thermal stimulation in the α chloralose and halothane anesthetized rat
Magnetic Resonance Imaging, 2008Co-Authors: Jane Lawrence, Patrick W Stroman, Krisztina L MaliszaAbstract:Patterns of neuronal activity in the spinal cord using functional magnetic resonance imaging during noxious (48°C) and innocuous (40°C) thermal stimulation of the rat forepaw were examined. The patterns of functional activity elicited by thermal stimuli were compared in α-chloralose- and halothane-anesthetized rats. Although the locations of active pixels were similar during both types of stimulation, the mean percentage signal change was higher during noxious stimulation in both anesthetic groups. Ipsilateral dorsal horn activity was evident during both noxious and innocuous stimulation in all animals. The greatest consistency of ipsilateral dorsal horn activity occurred at the C3 to C5 spinal cord segments in all groups. Consistent contralateral dorsal horn activity appeared in segments C6 to C8 in all groups. C-fos immunohistochemical staining confirmed the presence of neural activity in the spinal cords of all animals.