Thread: ChinaSCINet Update

  1. #1591
    No, was talking about the videos of my son that fti found on YouTube and to which he posted the links.

  2. #1592
    Quote Originally Posted by Chaz19 View Post
    I apologize if I've asked this question before, but is arm and hand restoration a higher hanging fruit than locomotion?
    Chaz,

    Hand function is not programmed in the spinal cord like walking and micturition. Distal hand function, in particular, is quite dependent on the motor cortex and the corticospinal tract. That is why stroke of the motor cortex, for example, have marked effects on hand function. However, it appears that the spinal cord has other mechanisms for improving hand function. Several spinal tracts are known to be able to substitute for the corticospinal tract. In the 1980's and early 1990's, a series of elegant studies by Alstermark, et al. [1-4], indicated that the propriospinal tract can substitute for loss of forepaw function in cats resulting from cutting the corticospinal tract, the rubrospinal tract, the reticulospinal tract, and the dorsal columns.

    So, the mechanisms of recovery and plasticity are different for the hand. In my opinion, one of the most important problems that we have not yet solved is repair of gray matter damage in the cervical and lumbosacral spinal cord. To do that, we have been working very hard on development of a lumbosacral spinal cord injury model and developing a immune-compatible source of neural stem cells to replace neurons in the spinal cord. This has been the primary focus of my laboratory for the past year.

    Wise.

    1. Alstermark B, Isa T and Tantisira B (1991). Integration in descending motor pathways controlling the forelimb in the cat. 18. Morphology, axonal projection and termination of collaterals from C3-C4 propriospinal neurones in the segment of origin. Exp Brain Res 84: 561-8. Department of Physiology, University of Goteborg, Sweden. The morphology of single C3-C4 propriospinal neurones (PNs) including the cell body, dendritic tree, axonal trajectory and the pattern of projection and termination of axonal collaterals in the C3-C4 segments was investigated by intra-somatic or intra-axonal injection of horseradish peroxidase. All the C3-C4 PNs could be antidromically activated from the lateral funicle in C6 and the lateral reticular nucleus but not from Th13. Another criterion was that they received monosynaptic excitation from corticospinal fibres in the contralateral pyramid. Twenty-four C3-C4 PNs were successfully stained. They were located in the lateral part of laminae VI-VIII except for two neurones which were located in lamina V and two in lamina IX. Five to eleven dendrites originated from the cell bodies and extended throughout laminae IV-VIII and even into the white matter in the transverse plane and up to 3 mm rostro-caudally. The axonal trajectory from the cell body was usually curved before reaching the lateral funicle. The bifurcation of the stem axon into a descending and an ascending branch was mostly observed in the white matter close to or at the border between the white and grey matter at the level of the cell body. The ascending and descending axonal branches maintained their location in the same part of the lateral funicle. Sixteen out of 24 stem axons gave off collaterals in the grey matter and/or in the white matter. One to five collaterals were given off from the axons in the grey matter.(ABSTRACT TRUNCATED AT 250 WORDS).
    2. Alstermark B, Lundberg A and Sasaki S (1984). Integration in descending motor pathways controlling the forelimb in the cat. 10. Inhibitory pathways to forelimb motoneurones via C3-C4 propriospinal neurones. Exp Brain Res 56: 279-92. A further analysis has been made of inhibitory pathways to motoneurones via C3-C4 propriospinal neurones (PNs). Intracellular recording was made from triceps brachi motoneurones and effects from higher centres and forelimb afferents on corticospinal IPSPs were investigated after transection of the corticospinal tract at the C5/C6 border. The shortest latencies of the IPSPs evoked by stimulation of the pyramid were as brief as those of the pyramidal EPSPs (Illert et al. 1977). It is postulated that the minimal linkage of the pyramidal IPSPs is disynaptic via inhibitory C3-C4 PNs projecting directly to motoneurones. It was confirmed that pyramidal IPSPs usually are depressed by volleys in forelimb motor axon collaterals (Illert and Tanaka 1978). A quantitative comparison was made of the recurrent depression of pyramidal IPSPs and of IPSPs caused by activation of the Ia inhibitory interneurones. The result support the hypothesis of two parallel inhibitory cortico-motoneuronal pathways via C3-C4 PNs, one disynaptic via the inhibitory PNs and the other trisynaptic via excitatory PNs and Ia inhibitory interneurones. Pyramidal volleys also evoked late IPSPs which in some cases were not depressed from forelimb motor axon collaterals. It is postulated that the late IPSPs are partly due to activation of inhibitory C3-C4 PNs. Disynaptic pyramidal IPSPs were effectively facilitated by volleys in rubro-, tecto- and reticulospinal fibres - but not from vestibulospinal fibres - showing a convergence from the former descending tracts on common inhibitory C3-C4 PNs. Projection from forelimb afferents and corticospinal fibres on common inhibitory C3-C4 PNs was revealed by strong facilitation of disynaptic pyramidal IPSPs from cutaneous forelimb afferents. No corresponding effect was evoked from C2 neck afferents. Stimulation in the lateral reticular nucleus (LRN) evoked monosynaptic IPSPs in some motoneurones. The results of threshold mapping in and around the LRN suggest that the IPSPs are caused by antidromic stimulation of ascending collaterals of inhibitory neurones also projecting to motoneurones, possibly the inhibitory C3-C4 PNs.
    3. Alstermark B, Lundberg A and Sasaki S (1984). Integration in descending motor pathways controlling the forelimb in the cat. 11. Inhibitory pathways from higher motor centres and forelimb afferents to C3-C4 propriospinal neurones. Exp Brain Res 56: 293-307. Intracellular recording was made in the C3-C4 segments from cell bodies of a previously described system of propriospinal neurones (PNs), which receive convergent monosynaptic excitation from different higher motor centres and mediate disynaptic excitation and inhibition from them to forelimb motoneurones. Inhibitory effects in these PNs have now been investigated with electrical stimulation of higher motor centres and forelimb nerves. Short-latency IPSPs were evoked by volleys in the cortico-, rubro- and tectospinal tracts and from the reticular formation. Latency measurements showed that those IPSPs which required temporal summation were disynaptically mediated. After transection of the corticospinal tract in C2, only small and infrequent disynaptic IPSPs were evoked from the pyramid. It is postulated that disynaptic pyramidal IPSPs only to a small extent are evoked by monosynaptic excitation of reticulospinal inhibitory neurones known to project directly to the PNs, and that they are mainly mediated by inhibitory interneurones in the C3-C4 segments. Tests with spatial facilitation revealed monosynaptic excitatory convergence from tecto-, rubro- and probably also from reticulospinal fibres on inhibitory interneurones monosynaptically excited from corticospinal fibres (interneuronal system I). Disynaptic IPSPs were also evoked in the great majority of the PNs by volleys in forelimb muscle and skin nerves. A short train of volleys was usually required to evoke these IPSPs from group I muscle afferents. In the case of cutaneous nerves and mixed nerves single volleys were often effective, and the lack of temporal facilitation of IPSPs produced by a train of volleys showed strong linkage from these nerves. The results obtained after transection of the dorsal column at different levels show that the relay is almost entirely rostral to the forelimb segments. Test with spatial facilitation revealed that interneurones monosynaptically activated from forelimb afferents receive convergent excitation from corticospinal but not or only weakly so from tecto- or rubrospinal fibres. There was also convergence from group I muscle afferents and low threshold cutaneous afferents on common interneurones. It is postulated that the disynaptic IPSPs from forelimb afferents are mediated by inhibitory interneurones (interneuronal system II) other than those receiving convergent descending excitation. Volleys in corticospinal fibres, in addition to the disynaptic IPSPs, evoke late IPSPs in the PNs. Similar late IPSPs were evoked from the ipsilateral forelimb by stimulation of the FRA.(ABSTRACT TRUNCATED AT 400 WORDS).
    4. Alstermark B, Lundberg A and Sasaki S (1984). Integration in descending motor pathways controlling the forelimb in the cat. 12. Interneurones which may mediate descending feed-forward inhibition and feed-back inhibition from the forelimb to C3-C4 propriospinal neurones. Exp Brain Res 56: 308-22. Extra- and intracellular recording was made from cells in the C3-C4 segments with the aim of finding interneurones of previously described inhibitory pathways to the C3-C4 propriospinal neurones, which may mediate descending feed-forward inhibition and feed-back inhibition from the forelimb, respectively. The lateral interneurones were found in the lateral part of lamina VII interspersed among the C3-C4 PNs and like them they receive convergent monosynaptic EPSPs and disynaptic IPSPs from the cortico-, rubro-, tecto- and reticulospinal tracts. Disynaptic IPSPs, but only rarely monosynaptic EPSPs, are evoked in them from forelimb nerves. The lateral interneurones do not project to the lateral reticular nucleus (LRN). The medial interneurones were found medially in laminae V and VI in a region where volleys in forelimb nerves evoke extracellular monosynaptic focal potentials (Rosen 1969). There is somatotopic organization of the projection from the forelimb to this region. Many neurones are strongly monosynaptically excited from group I muscle or/and cutaneous forelimb afferents. In addition, late discharges are evoked in many cells from cutaneous afferents and high threshold muscle afferents. Corticospinal volleys evoked monosynaptic excitation in the great majority of these cells and usually also late EPSPs or IPSPs. Typically, rubrospinal and tectospinal volleys evoked neither monosynaptic excitation nor late effects as those elicited from corticospinal fibres. In some of the interneurones, IPSPs were evoked from forelimb nerves. About 20% of the medial "interneurones" have an ascending projection to the caudal brain stem. Threshold mapping for antidromic stimulation revealed termination in the main cuneate nucleus, the external cuneate nucleus and/or the LRN and also a branch projecting to more rostral levels in the brain. A few of the neurones in the medial region are PNs projecting to the forelimb segments. It is postulated that interneurones both of the lateral and medial type are inhibitory and project to the C3-C4 PNs. It is further postulated that the former are intercalated in the descending feed-forward inhibitory pathway to the C3-C4 PNs and the latter in the feed-back inhibitory pathway from the forelimb to these PNs. The role of feed-forward and feed-back inhibition of transmission from the brain to forelimb motoneurones via the C3-C4 PNs is discussed.
    Last edited by Wise Young; 02-07-2013 at 08:44 AM.

  3. #1593
    Quote Originally Posted by rjg View Post
    This appears to conflict with "Mamadavid's" posts. She seems to be saying that the man in the video is her son. Who was about four years into his injury, but received no cells. And went to China as an incomplete. This seems to be a key point. What's going on?
    rjg, this is one of the subjects of our clinical trial. MamaDavid's son was not in our study. All the subjects in our trial are ASIA A complete spinal cord injuries.

    Wise.

  4. #1594
    Dr.Young,
    Hi, hope you are doing fine , thanks for everything you are doing. one question (I am not sure if I understood it correctly from the video) ;With regard to The woman that you said she had the worse sci you have ever seen, and was ASIA A COMPLETE , and now she is walking which is really amazing indeed ; Did she only received UNTETHERING SURGERY , or in addition to untethering , she received umbilical cord stem cells treatments too? That case was really amazing .
    Thank you

  5. #1595
    Quote Originally Posted by kz View Post
    Dr.Young,
    Hi, thanks for everything you are doing. one question (I am not sure if I understood it correctly from the video) ;With regard to The woman that you said she had the worse sci you have ever seen, and was ASIA A COMPLETE , and now she is walking which is really amazing indeed ; Did she only received UNTETHERING SURGERY , or in addition to untethering , she received umbilical cord stem cells too? That case was really amazing .
    Thank you
    She was not one of the patients in our study and therefore did not receive our umbilical cord blood cell therapy. To my knowledge, she received decompression and untethering surgery. I presented the case because it was one of the reasons why we decided to include an untethering control group to our planned phase III trial.

    Wise.

  6. #1596

  7. #1597
    pr in a post you had said that regeneration is faster in cervical lesion






    Quote Originally Posted by Wise Young View Post
    Chaz,

    Hand function is not programmed in the spinal cord like walking and micturition. Distal hand function, in particular, is quite dependent on the motor cortex and the corticospinal tract. That is why stroke of the motor cortex, for example, have marked effects on hand function. However, it appears that the spinal cord has other mechanisms for improving hand function. Several spinal tracts are known to be able to substitute for the corticospinal tract. In the 1980's and early 1990's, a series of elegant studies by Alstermark, et al. [1-4], indicated that the propriospinal tract can substitute for loss of forepaw function in cats resulting from cutting the corticospinal tract, the rubrospinal tract, the reticulospinal tract, and the dorsal columns.

    So, the mechanisms of recovery and plasticity are different for the hand. In my opinion, one of the most important problems that we have not yet solved is repair of gray matter damage in the cervical and lumbosacral spinal cord. To do that, we have been working very hard on development of a lumbosacral spinal cord injury model and developing a immune-compatible source of neural stem cells to replace neurons in the spinal cord. This has been the primary focus of my laboratory for the past year.

    Wise.

    1. Alstermark B, Isa T and Tantisira B (1991). Integration in descending motor pathways controlling the forelimb in the cat. 18. Morphology, axonal projection and termination of collaterals from C3-C4 propriospinal neurones in the segment of origin. Exp Brain Res 84: 561-8. Department of Physiology, University of Goteborg, Sweden. The morphology of single C3-C4 propriospinal neurones (PNs) including the cell body, dendritic tree, axonal trajectory and the pattern of projection and termination of axonal collaterals in the C3-C4 segments was investigated by intra-somatic or intra-axonal injection of horseradish peroxidase. All the C3-C4 PNs could be antidromically activated from the lateral funicle in C6 and the lateral reticular nucleus but not from Th13. Another criterion was that they received monosynaptic excitation from corticospinal fibres in the contralateral pyramid. Twenty-four C3-C4 PNs were successfully stained. They were located in the lateral part of laminae VI-VIII except for two neurones which were located in lamina V and two in lamina IX. Five to eleven dendrites originated from the cell bodies and extended throughout laminae IV-VIII and even into the white matter in the transverse plane and up to 3 mm rostro-caudally. The axonal trajectory from the cell body was usually curved before reaching the lateral funicle. The bifurcation of the stem axon into a descending and an ascending branch was mostly observed in the white matter close to or at the border between the white and grey matter at the level of the cell body. The ascending and descending axonal branches maintained their location in the same part of the lateral funicle. Sixteen out of 24 stem axons gave off collaterals in the grey matter and/or in the white matter. One to five collaterals were given off from the axons in the grey matter.(ABSTRACT TRUNCATED AT 250 WORDS).
    2. Alstermark B, Lundberg A and Sasaki S (1984). Integration in descending motor pathways controlling the forelimb in the cat. 10. Inhibitory pathways to forelimb motoneurones via C3-C4 propriospinal neurones. Exp Brain Res 56: 279-92. A further analysis has been made of inhibitory pathways to motoneurones via C3-C4 propriospinal neurones (PNs). Intracellular recording was made from triceps brachi motoneurones and effects from higher centres and forelimb afferents on corticospinal IPSPs were investigated after transection of the corticospinal tract at the C5/C6 border. The shortest latencies of the IPSPs evoked by stimulation of the pyramid were as brief as those of the pyramidal EPSPs (Illert et al. 1977). It is postulated that the minimal linkage of the pyramidal IPSPs is disynaptic via inhibitory C3-C4 PNs projecting directly to motoneurones. It was confirmed that pyramidal IPSPs usually are depressed by volleys in forelimb motor axon collaterals (Illert and Tanaka 1978). A quantitative comparison was made of the recurrent depression of pyramidal IPSPs and of IPSPs caused by activation of the Ia inhibitory interneurones. The result support the hypothesis of two parallel inhibitory cortico-motoneuronal pathways via C3-C4 PNs, one disynaptic via the inhibitory PNs and the other trisynaptic via excitatory PNs and Ia inhibitory interneurones. Pyramidal volleys also evoked late IPSPs which in some cases were not depressed from forelimb motor axon collaterals. It is postulated that the late IPSPs are partly due to activation of inhibitory C3-C4 PNs. Disynaptic pyramidal IPSPs were effectively facilitated by volleys in rubro-, tecto- and reticulospinal fibres - but not from vestibulospinal fibres - showing a convergence from the former descending tracts on common inhibitory C3-C4 PNs. Projection from forelimb afferents and corticospinal fibres on common inhibitory C3-C4 PNs was revealed by strong facilitation of disynaptic pyramidal IPSPs from cutaneous forelimb afferents. No corresponding effect was evoked from C2 neck afferents. Stimulation in the lateral reticular nucleus (LRN) evoked monosynaptic IPSPs in some motoneurones. The results of threshold mapping in and around the LRN suggest that the IPSPs are caused by antidromic stimulation of ascending collaterals of inhibitory neurones also projecting to motoneurones, possibly the inhibitory C3-C4 PNs.
    3. Alstermark B, Lundberg A and Sasaki S (1984). Integration in descending motor pathways controlling the forelimb in the cat. 11. Inhibitory pathways from higher motor centres and forelimb afferents to C3-C4 propriospinal neurones. Exp Brain Res 56: 293-307. Intracellular recording was made in the C3-C4 segments from cell bodies of a previously described system of propriospinal neurones (PNs), which receive convergent monosynaptic excitation from different higher motor centres and mediate disynaptic excitation and inhibition from them to forelimb motoneurones. Inhibitory effects in these PNs have now been investigated with electrical stimulation of higher motor centres and forelimb nerves. Short-latency IPSPs were evoked by volleys in the cortico-, rubro- and tectospinal tracts and from the reticular formation. Latency measurements showed that those IPSPs which required temporal summation were disynaptically mediated. After transection of the corticospinal tract in C2, only small and infrequent disynaptic IPSPs were evoked from the pyramid. It is postulated that disynaptic pyramidal IPSPs only to a small extent are evoked by monosynaptic excitation of reticulospinal inhibitory neurones known to project directly to the PNs, and that they are mainly mediated by inhibitory interneurones in the C3-C4 segments. Tests with spatial facilitation revealed monosynaptic excitatory convergence from tecto-, rubro- and probably also from reticulospinal fibres on inhibitory interneurones monosynaptically excited from corticospinal fibres (interneuronal system I). Disynaptic IPSPs were also evoked in the great majority of the PNs by volleys in forelimb muscle and skin nerves. A short train of volleys was usually required to evoke these IPSPs from group I muscle afferents. In the case of cutaneous nerves and mixed nerves single volleys were often effective, and the lack of temporal facilitation of IPSPs produced by a train of volleys showed strong linkage from these nerves. The results obtained after transection of the dorsal column at different levels show that the relay is almost entirely rostral to the forelimb segments. Test with spatial facilitation revealed that interneurones monosynaptically activated from forelimb afferents receive convergent excitation from corticospinal but not or only weakly so from tecto- or rubrospinal fibres. There was also convergence from group I muscle afferents and low threshold cutaneous afferents on common interneurones. It is postulated that the disynaptic IPSPs from forelimb afferents are mediated by inhibitory interneurones (interneuronal system II) other than those receiving convergent descending excitation. Volleys in corticospinal fibres, in addition to the disynaptic IPSPs, evoke late IPSPs in the PNs. Similar late IPSPs were evoked from the ipsilateral forelimb by stimulation of the FRA.(ABSTRACT TRUNCATED AT 400 WORDS).
    4. Alstermark B, Lundberg A and Sasaki S (1984). Integration in descending motor pathways controlling the forelimb in the cat. 12. Interneurones which may mediate descending feed-forward inhibition and feed-back inhibition from the forelimb to C3-C4 propriospinal neurones. Exp Brain Res 56: 308-22. Extra- and intracellular recording was made from cells in the C3-C4 segments with the aim of finding interneurones of previously described inhibitory pathways to the C3-C4 propriospinal neurones, which may mediate descending feed-forward inhibition and feed-back inhibition from the forelimb, respectively. The lateral interneurones were found in the lateral part of lamina VII interspersed among the C3-C4 PNs and like them they receive convergent monosynaptic EPSPs and disynaptic IPSPs from the cortico-, rubro-, tecto- and reticulospinal tracts. Disynaptic IPSPs, but only rarely monosynaptic EPSPs, are evoked in them from forelimb nerves. The lateral interneurones do not project to the lateral reticular nucleus (LRN). The medial interneurones were found medially in laminae V and VI in a region where volleys in forelimb nerves evoke extracellular monosynaptic focal potentials (Rosen 1969). There is somatotopic organization of the projection from the forelimb to this region. Many neurones are strongly monosynaptically excited from group I muscle or/and cutaneous forelimb afferents. In addition, late discharges are evoked in many cells from cutaneous afferents and high threshold muscle afferents. Corticospinal volleys evoked monosynaptic excitation in the great majority of these cells and usually also late EPSPs or IPSPs. Typically, rubrospinal and tectospinal volleys evoked neither monosynaptic excitation nor late effects as those elicited from corticospinal fibres. In some of the interneurones, IPSPs were evoked from forelimb nerves. About 20% of the medial "interneurones" have an ascending projection to the caudal brain stem. Threshold mapping for antidromic stimulation revealed termination in the main cuneate nucleus, the external cuneate nucleus and/or the LRN and also a branch projecting to more rostral levels in the brain. A few of the neurones in the medial region are PNs projecting to the forelimb segments. It is postulated that interneurones both of the lateral and medial type are inhibitory and project to the C3-C4 PNs. It is further postulated that the former are intercalated in the descending feed-forward inhibitory pathway to the C3-C4 PNs and the latter in the feed-back inhibitory pathway from the forelimb to these PNs. The role of feed-forward and feed-back inhibition of transmission from the brain to forelimb motoneurones via the C3-C4 PNs is discussed.
    JustaDollarPlease.org

  8. #1598
    Quote Originally Posted by kz View Post
    dr.young,
    hi, hope you are doing fine , thanks for everything you are doing. One question (i am not sure if i understood it correctly from the video) ;with regard to the woman that you said she had the worse sci you have ever seen, and was asia a complete , and now she is walking which is really amazing indeed ; did she only received untethering surgery , or in addition to untethering , she received umbilical cord stem cells treatments too? That case was really amazing .
    Thank you



    i heard nothing on this woman
    about which video spoke to you?
    JustaDollarPlease.org

  9. #1599
    fti,
    see the post that "Jim" posted on this thread on 2-2-2013 . I think it is his post no. 6856.
    there is a link there for that video that Dr. young is speaking . the post is on page 156 of this thread (by Jim) .

  10. #1600
    Thk kz a how many minutes of the video?
    JustaDollarPlease.org

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