The Experts below are selected from a list of 174 Experts worldwide ranked by ideXlab platform

Martin E. Schwab - One of the best experts on this subject based on the ideXlab platform.

  • Anti-Nogo on the go: from AnimAl models to A clinicAl triAl.
    Annals of the New York Academy of Sciences, 2020
    Co-Authors: Björn Zörner, Martin E. Schwab
    Abstract:

    SmAll lesions of the Adult centrAl nervous system (CNS) often hAve A good prognosis with extensive functionAl recovery bAsed in pArt on spontAneous neuritic sprouting And reArrAngements of projections. This is well documented for the cortex, but these chAnges cAn Also occur in the spinAl cord. Nogo-A is A protein present in CNS myelin thAt inhibits neurite growth. Models of spinAl cord injury (SCI) in rAts And mAcAque monkeys demonstrAte thAt treAtment with function-blocking Antibodies of Nogo-A results in An upregulAtion of growth-specific proteins, enhAnced regenerAtive And compensAtory sprouting of fibers, And the formAtion of new functionAl connections in the spinAl cord. In AnimAls with unilAterAl sensorimotor cortex lesions followed by Nogo-A Antibody treAtment, fibers from the intAct corticofugAl system crossed the midline, supplying innervAtion to the denervAted brAin stem or spinAl cord. BehAviorAl tests showed mArked improvements of functionAl recovery in the Nogo-A Antibody treAted spinAl cord- or brAin-injured AnimAls. A PhAse I clinicAl triAl Applying Anti-Nogo-A Antibody to subjects with Acute SCI hAs been successfully conducted And A multicentric, multinAtionAl PhAse II triAl is currently in prepArAtion.

  • Long-term motor corticAl mAp chAnges following unilAterAl lesion of the hAnd representAtion in the motor cortex in mAcAque monkeys showing functionAl recovery of hAnd functions.
    Restorative Neurology and Neuroscience, 2020
    Co-Authors: Alexander F. Wyss, Martin E. Schwab, Eric M Rouiller, Adjia Hamadjida, Julie Savidan, Shahid Bashir, Abderaouf Belhaj-saif
    Abstract:

    Purpose: How Are motor mAps modified within And in the immediAte vicinity of A dAmAged zone in the motor cortex of non-humAn primAtes? Methods: In eight Adult mAcAque monkeys subjected to A restricted chemicAl lesion of the hAnd AreA in the primAry motor cortex (M1), motor mAps were estAblished using intrAcorticAl micro-stimulAtion (ICMS) techniques. The monkeys were subdivided into five AnimAls without treAtment, whereAs three monkeys received An Anti-Nogo-A Antibody treAtment. Results: Following permAnent M1 injury, the lesion territory becAme lArgely non micro-excitAble severAl months post-lesion, in spite of some recovery of hAnd function. Few sites within the lesion territory remAined excitAble, though irrespective to the degree of functionAl recovery. Around the lesion in M1, there wAs no reAllocAtion of proximAl shoulder/Arm territories into distAl hAnd functions. However, ICMS delivered At suprA-threshold intensities in these proximAl territories elicited digit movements. Post-lesion ICMS thresholds to elicit movements of forelimb muscle territories increAsed, independently from the degree of functionAl recovery. Further behAviourAl evidence for An enhAncement of functionAl recovery promoted by the Anti-Nogo-A Antibody treAtment is provided. Conclusion: The degree of functionAl recovery is not relAted to A reorgAnizAtion of motor mAps within, And in the vicinity of, A M1 lesion.

  • TArgeting TherApeutic Antibodies to the CNS: A CompArAtive Study of IntrAthecAl, IntrAvenous, And SubcutAneous Anti-Nogo A Antibody TreAtment After Stroke in RAts
    Neurotherapeutics, 2020
    Co-Authors: Anna-sophia Wahl, Daphne Correa, Stefan Imobersteg, Michael Andreas Maurer, Julia Kaiser, Marc Aurel Augath, Martin E. Schwab
    Abstract:

    Antibody-bAsed therApeutics tArgeting CNS Antigens emerge As promising treAtments in neurology. However, Access to the CNS is limited by the blood–brAin bArrier. We exAmined the effects of A neurite growth-enhAncing Anti-Nogo A Antibody therApy following 3 routes of AdministrAtion—intrAthecAl (i.t.), intrAvenous (i.v.), And subcutAneous (s.c.)—After lArge photothrombotic strokes in Adult rAts. IntrAthecAl treAtment of full-length IgG Anti-Nogo A Antibodies enhAnced recovery of the grAsping function, but intrAvenous or subcutAneous AdministrAtion hAd no detectAble effect in spite of lArge Amounts of Antibodies in the peripherAl circulAtion. Thus, in contrAst to intrAvenous And subcutAneous delivery, intrAthecAl AdministrAtion is An effective And reliAble wAy to tArget CNS Antigens. Our dAtA reveAl thAt Antibody delivery to the CNS is fAr from triviAl. While intrAthecAl ApplicAtion is feAsible And guArAntees defined Antibody doses in the effective rAnge for A biologicAl function, the identificAtion And estAblishment of eAsier routes of AdministrAtion remAins An importAnt tAsk to fAcilitAte Antibody-bAsed future therApies of CNS disorders.

  • Recovery After spinAl cord injury is enhAnced by Anti-Nogo-A Antibody therApy — from AnimAl models to clinicAl triAls
    Current Opinion in Physiology, 2020
    Co-Authors: Andrea M. Sartori, Anna-sophie Hofer, Martin E. Schwab
    Abstract:

    The Ability of the centrAl nervous system to regenerAte over long distAnces After A lesion is restricted by the presence of physicAl And biochemicAl bArriers, neuronAl growth progrAms chAnges, And A non-permissive tissue environment. The myelin-derived membrAne protein Nogo-A exerts repulsive And neurite growth-inhibitory functions thAt cAn criticAlly Affect the AxonAl regenerAtion cApAbility. Suppression of Nogo-A signAling viA function-blocking Antibodies, receptor-bodies or genetic mAnipulAtion showed A relevAnt increAse in the functionAl recovery including locomotion And lower urinAry trAct function in spinAl cord injured rodents As well As hAnd function in monkeys. The currently on-going phAse II clinicAl triAls will elucidAte the potentiAl relevAnce of Nogo-A suppression for A novel therApeutic mAnAgement of spinAl cord injury in humAn pAtients.

  • recovery After spinAl cord injury is enhAnced by Anti Nogo A Antibody therApy from AnimAl models to clinicAl triAls
    Current Opinion in Physiology, 2020
    Co-Authors: Martin E. Schwab, Andrea M. Sartori, Anna-sophie Hofer
    Abstract:

    The Ability of the centrAl nervous system to regenerAte over long distAnces After A lesion is restricted by the presence of physicAl And biochemicAl bArriers, neuronAl growth progrAms chAnges, And A non-permissive tissue environment. The myelin-derived membrAne protein Nogo-A exerts repulsive And neurite growth-inhibitory functions thAt cAn criticAlly Affect the AxonAl regenerAtion cApAbility. Suppression of Nogo-A signAling viA function-blocking Antibodies, receptor-bodies or genetic mAnipulAtion showed A relevAnt increAse in the functionAl recovery including locomotion And lower urinAry trAct function in spinAl cord injured rodents As well As hAnd function in monkeys. The currently on-going phAse II clinicAl triAls will elucidAte the potentiAl relevAnce of Nogo-A suppression for A novel therApeutic mAnAgement of spinAl cord injury in humAn pAtients.

Eric M Rouiller - One of the best experts on this subject based on the ideXlab platform.

  • Long-term motor corticAl mAp chAnges following unilAterAl lesion of the hAnd representAtion in the motor cortex in mAcAque monkeys showing functionAl recovery of hAnd functions.
    Restorative Neurology and Neuroscience, 2020
    Co-Authors: Alexander F. Wyss, Martin E. Schwab, Eric M Rouiller, Adjia Hamadjida, Julie Savidan, Shahid Bashir, Abderaouf Belhaj-saif
    Abstract:

    Purpose: How Are motor mAps modified within And in the immediAte vicinity of A dAmAged zone in the motor cortex of non-humAn primAtes? Methods: In eight Adult mAcAque monkeys subjected to A restricted chemicAl lesion of the hAnd AreA in the primAry motor cortex (M1), motor mAps were estAblished using intrAcorticAl micro-stimulAtion (ICMS) techniques. The monkeys were subdivided into five AnimAls without treAtment, whereAs three monkeys received An Anti-Nogo-A Antibody treAtment. Results: Following permAnent M1 injury, the lesion territory becAme lArgely non micro-excitAble severAl months post-lesion, in spite of some recovery of hAnd function. Few sites within the lesion territory remAined excitAble, though irrespective to the degree of functionAl recovery. Around the lesion in M1, there wAs no reAllocAtion of proximAl shoulder/Arm territories into distAl hAnd functions. However, ICMS delivered At suprA-threshold intensities in these proximAl territories elicited digit movements. Post-lesion ICMS thresholds to elicit movements of forelimb muscle territories increAsed, independently from the degree of functionAl recovery. Further behAviourAl evidence for An enhAncement of functionAl recovery promoted by the Anti-Nogo-A Antibody treAtment is provided. Conclusion: The degree of functionAl recovery is not relAted to A reorgAnizAtion of motor mAps within, And in the vicinity of, A M1 lesion.

  • combined with Anti Nogo A Antibody treAtment bdnf did not compensAte the extrA deleterious motor effect cAused by lArge size cervicAl cord hemisection in Adult mAcAques
    CNS Neuroscience & Therapeutics, 2020
    Co-Authors: Marielaure Beaud, Martin E. Schwab, Eric M Rouiller, Jocelyne Bloch, Eric Schmidlin
    Abstract:

    In spinAl cord injured Adult mAmmAls, neutrAlizing the neurite growth inhibitor Nogo-A with Antibodies promotes AxonAl regenerAtion And functionAl recovery, Although AxonAl regenerAtion is limited in length. Neurotrophic fActors such As BDNF stimulAte neurite outgrowth And protect Axotomized neurons. CAn the effects obtAined by neutrAlizing Nogo-A, inducing An environment fAvorAble for AxonAl sprouting, be strengthened by Adding BDNF? A unilAterAl incomplete hemicord lesion At C7 level interrupted the mAin corticospinAl component in three groups of Adult mAcAque monkeys: control monkeys (n = 6), Anti-Nogo-A Antibody-treAted monkeys (n = 7), And Anti-Nogo-A Antibody And BDNF-treAted monkeys (n = 5). The functionAl recovery of mAnuAl dexterity wAs significAntly different between the 3 groups of monkeys, the lowest in the control group. WhereAs the Anti-Nogo-A Antibody-treAted AnimAls returned to mAnuAl dexterity performAnces close to prelesion ones, irrespective of lesion size, both the control And the Anti-Nogo-A/BDNF AnimAls presented A limited functionAl recovery. In the control group, the limited spontAneous functionAl recovery depended on lesion size, A dependence Absent in the combined treAtment group (Anti-Nogo-A Antibody And BDNF). The functionAl recovery in the lAtter group wAs significAntly lower thAn in Anti-Nogo-A Antibody-treAted monkeys, Although the lesion wAs lArger in three out of the five monkeys in the combined treAtment group.

  • CorticotectAl Projections From the Premotor or PrimAry Motor Cortex After CorticAl Lesion or PArkinsoniAn Symptoms in Adult MAcAque Monkeys: A Pilot TrAcing Study.
    Frontiers in Neuroanatomy, 2019
    Co-Authors: Michela Fregosi, Martin E. Schwab, Jocelyne Bloch, Alessandro Contestabile, Simon Badoud, Simon Borgognon, Jérôme Cottet, Jean-françois Brunet, Eric M Rouiller
    Abstract:

    : The corticotectAl projections, together with the corticobulbAr (corticoreticulAr) projections, work in pArAllel with the corticospinAl trAct (CST) to influence motoneurons in the spinAl cord both directly And indirectly viA the brAinstem descending pAthwAys. The tectospinAl trAct (TST) originAtes in the deep lAyers of the superior colliculus. In the present study, we AnAlyzed the corticotectAl projections from two motor corticAl AreAs, nAmely the premotor cortex (PM) And the primAry motor cortex (M1) in eight mAcAque monkeys subjected to either A corticAl lesion of the hAnd AreA in M1 (n = 4) or PArkinson's diseAse-like symptoms PD (n = 4). A subgroup of monkeys with corticAl lesion wAs subjected to Anti-Nogo-A Antibody treAtment whereAs All PD monkeys were trAnsplAnted with Autologous NeurAl Cell Ecosystems (ANCEs). The AnterogrAde trAcer BDA wAs used to lAbel the AxonAl boutons both en pAssAnt And terminAux in the ipsilAterAl superior colliculus. IndividuAl AxonAl boutons were chArted in the different lAyers of the superior colliculus. In intAct AnimAls, we previously observed thAt corticotectAl projections were denser when originAting from PM thAn from M1. In the present M1 lesioned monkeys, As compAred to intAct ones the corticotectAl projection originAting from PM wAs decreAsed when treAted with Anti-Nogo-A Antibody but not in untreAted monkeys. In PD-like symptoms' monkeys, on the other hAnd, there wAs no consistent chAnge Affecting the corticotectAl projection As compAred to intAct monkeys. The present pilot study overAll suggests thAt the corticotectAl projection is less Affected by M1 lesion or PD symptoms thAn the corticoreticulAr projection previously reported in the sAme AnimAls.

  • ChAnges of motor corticobulbAr projections following different lesion types Affecting the centrAl nervous system in Adult mAcAque monkeys.
    European Journal of Neuroscience, 2018
    Co-Authors: Michela Fregosi, Martin E. Schwab, Jocelyne Bloch, Alessandro Contestabile, Simon Badoud, Simon Borgognon, Jérôme Cottet, Jean-françois Brunet, Eric M Rouiller
    Abstract:

    : FunctionAl recovery from centrAl nervous system injury is likely to be pArtly due to A reArrAngement of neurAl circuits. In this context, the corticobulbAr (corticoreticulAr) motor projections onto different nuclei of the ponto-medullAry reticulAr formAtion (PMRF) were investigAted in 13 Adult mAcAque monkeys After either, primAry motor cortex injury (MCI) in the hAnd AreA, or spinAl cord injury (SCI) or PArkinson's diseAse-like lesions of the nigro-striAtAl dopAminergic system (PD). A subgroup of AnimAls in both MCI And SCI groups wAs treAted with neurite growth promoting Anti-Nogo-A Antibodies, whereAs All PD AnimAls were treAted with Autologous neurAl cell ecosystems (ANCE). The AnterogrAde trAcer BDA wAs injected either in the premotor cortex (PM) or in the primAry motor cortex (M1) to lAbel And quAntify corticobulbAr AxonAl boutons terminAux And en pAssAnt in PMRF. As compAred to intAct AnimAls, After MCI the density of corticobulbAr projections from PM wAs strongly reduced but mAintAined their lAterAlity dominAnce (ipsilAterAl), both in the presence or Absence of Anti-Nogo-A Antibody treAtment. In contrAst, the density of corticobulbAr projections from M1 wAs increAsed following opposite hemi-section of the cervicAl cord (At C7 level) And Anti-Nogo-A Antibody treAtment, with mAintenAnce of contrAlAterAl lAterAlity biAs. In PD monkeys, the density of corticobulbAr projections from PM wAs strongly reduced, As well As thAt from M1, but to A lesser extent. In conclusion, the densities of corticobulbAr projections from PM or M1 were Affected in A vAriAble mAnner, depending on the type of lesion/pAthology And the treAtment Aimed to enhAnce functionAl recovery.

  • Influence of Anti-Nogo-A Antibody treAtment on the reorgAnizAtion of cAllosAl connectivity of the premotor corticAl AreAs following unilAterAl lesion of primAry motor cortex (M1) in Adult mAcAque monkeys
    Experimental Brain Research, 2012
    Co-Authors: Adjia Hamadjida, Martin E. Schwab, Alexander F. Wyss, Abderaouf Belhaj-saif, Eric M Rouiller
    Abstract:

    Following unilAterAl lesion of the primAry motor cortex, the reorgAnizAtion of cAllosAl projections from the intAct hemisphere to the ipsilesionAl premotor cortex (PM) wAs investigAted in 7 Adult mAcAque monkeys, in Absence of treAtment (control; n  = 4) or treAted with function blocking Antibodies AgAinst the neurite growth inhibitory protein Nogo-A ( n  = 3). After functionAl recovery, though incomplete, the trAcer biotinylAted dextrAn Amine (BDA) wAs injected in the ipsilesionAl PM. RetrogrAdely lAbelled neurons were plotted in the intAct hemisphere And their number wAs normAlized with respect to the volume of the core of BDA injection sites. (1) The cAllosAl projections to PM in the controls originAte mAinly from homotypic PM AreAs And, but to A somewhAt lesser extent, from the mesiAl cortex (cingulAte And supplementAry motor AreAs). (2) In the lesioned Anti-Nogo-A Antibody-treAted monkeys, the normAlized number of cAllosAl retrogrAdely lAbelled neurons wAs up to severAl folds higher thAn in controls, especiAlly in the homotypic PM AreAs. (3) Except one control with A smAll lesion And A limited, trAnsient deficit, the Anti-Nogo-A Antibody-treAted monkeys recovered to neArly bAseline levels of performAnce (73–90 %), in contrAst to persistent deficits in the control monkeys. These results Are consistent with A sprouting And/or spAring of cAllosAl Axons promoted by the Anti-Nogo-A Antibody treAtment After lesion of the primAry motor cortex, As compAred to untreAted monkeys.

Jocelyne Bloch - One of the best experts on this subject based on the ideXlab platform.

  • combined with Anti Nogo A Antibody treAtment bdnf did not compensAte the extrA deleterious motor effect cAused by lArge size cervicAl cord hemisection in Adult mAcAques
    CNS Neuroscience & Therapeutics, 2020
    Co-Authors: Marielaure Beaud, Martin E. Schwab, Eric M Rouiller, Jocelyne Bloch, Eric Schmidlin
    Abstract:

    In spinAl cord injured Adult mAmmAls, neutrAlizing the neurite growth inhibitor Nogo-A with Antibodies promotes AxonAl regenerAtion And functionAl recovery, Although AxonAl regenerAtion is limited in length. Neurotrophic fActors such As BDNF stimulAte neurite outgrowth And protect Axotomized neurons. CAn the effects obtAined by neutrAlizing Nogo-A, inducing An environment fAvorAble for AxonAl sprouting, be strengthened by Adding BDNF? A unilAterAl incomplete hemicord lesion At C7 level interrupted the mAin corticospinAl component in three groups of Adult mAcAque monkeys: control monkeys (n = 6), Anti-Nogo-A Antibody-treAted monkeys (n = 7), And Anti-Nogo-A Antibody And BDNF-treAted monkeys (n = 5). The functionAl recovery of mAnuAl dexterity wAs significAntly different between the 3 groups of monkeys, the lowest in the control group. WhereAs the Anti-Nogo-A Antibody-treAted AnimAls returned to mAnuAl dexterity performAnces close to prelesion ones, irrespective of lesion size, both the control And the Anti-Nogo-A/BDNF AnimAls presented A limited functionAl recovery. In the control group, the limited spontAneous functionAl recovery depended on lesion size, A dependence Absent in the combined treAtment group (Anti-Nogo-A Antibody And BDNF). The functionAl recovery in the lAtter group wAs significAntly lower thAn in Anti-Nogo-A Antibody-treAted monkeys, Although the lesion wAs lArger in three out of the five monkeys in the combined treAtment group.

  • CorticotectAl Projections From the Premotor or PrimAry Motor Cortex After CorticAl Lesion or PArkinsoniAn Symptoms in Adult MAcAque Monkeys: A Pilot TrAcing Study.
    Frontiers in Neuroanatomy, 2019
    Co-Authors: Michela Fregosi, Martin E. Schwab, Jocelyne Bloch, Alessandro Contestabile, Simon Badoud, Simon Borgognon, Jérôme Cottet, Jean-françois Brunet, Eric M Rouiller
    Abstract:

    : The corticotectAl projections, together with the corticobulbAr (corticoreticulAr) projections, work in pArAllel with the corticospinAl trAct (CST) to influence motoneurons in the spinAl cord both directly And indirectly viA the brAinstem descending pAthwAys. The tectospinAl trAct (TST) originAtes in the deep lAyers of the superior colliculus. In the present study, we AnAlyzed the corticotectAl projections from two motor corticAl AreAs, nAmely the premotor cortex (PM) And the primAry motor cortex (M1) in eight mAcAque monkeys subjected to either A corticAl lesion of the hAnd AreA in M1 (n = 4) or PArkinson's diseAse-like symptoms PD (n = 4). A subgroup of monkeys with corticAl lesion wAs subjected to Anti-Nogo-A Antibody treAtment whereAs All PD monkeys were trAnsplAnted with Autologous NeurAl Cell Ecosystems (ANCEs). The AnterogrAde trAcer BDA wAs used to lAbel the AxonAl boutons both en pAssAnt And terminAux in the ipsilAterAl superior colliculus. IndividuAl AxonAl boutons were chArted in the different lAyers of the superior colliculus. In intAct AnimAls, we previously observed thAt corticotectAl projections were denser when originAting from PM thAn from M1. In the present M1 lesioned monkeys, As compAred to intAct ones the corticotectAl projection originAting from PM wAs decreAsed when treAted with Anti-Nogo-A Antibody but not in untreAted monkeys. In PD-like symptoms' monkeys, on the other hAnd, there wAs no consistent chAnge Affecting the corticotectAl projection As compAred to intAct monkeys. The present pilot study overAll suggests thAt the corticotectAl projection is less Affected by M1 lesion or PD symptoms thAn the corticoreticulAr projection previously reported in the sAme AnimAls.

  • ChAnges of motor corticobulbAr projections following different lesion types Affecting the centrAl nervous system in Adult mAcAque monkeys.
    European Journal of Neuroscience, 2018
    Co-Authors: Michela Fregosi, Martin E. Schwab, Jocelyne Bloch, Alessandro Contestabile, Simon Badoud, Simon Borgognon, Jérôme Cottet, Jean-françois Brunet, Eric M Rouiller
    Abstract:

    : FunctionAl recovery from centrAl nervous system injury is likely to be pArtly due to A reArrAngement of neurAl circuits. In this context, the corticobulbAr (corticoreticulAr) motor projections onto different nuclei of the ponto-medullAry reticulAr formAtion (PMRF) were investigAted in 13 Adult mAcAque monkeys After either, primAry motor cortex injury (MCI) in the hAnd AreA, or spinAl cord injury (SCI) or PArkinson's diseAse-like lesions of the nigro-striAtAl dopAminergic system (PD). A subgroup of AnimAls in both MCI And SCI groups wAs treAted with neurite growth promoting Anti-Nogo-A Antibodies, whereAs All PD AnimAls were treAted with Autologous neurAl cell ecosystems (ANCE). The AnterogrAde trAcer BDA wAs injected either in the premotor cortex (PM) or in the primAry motor cortex (M1) to lAbel And quAntify corticobulbAr AxonAl boutons terminAux And en pAssAnt in PMRF. As compAred to intAct AnimAls, After MCI the density of corticobulbAr projections from PM wAs strongly reduced but mAintAined their lAterAlity dominAnce (ipsilAterAl), both in the presence or Absence of Anti-Nogo-A Antibody treAtment. In contrAst, the density of corticobulbAr projections from M1 wAs increAsed following opposite hemi-section of the cervicAl cord (At C7 level) And Anti-Nogo-A Antibody treAtment, with mAintenAnce of contrAlAterAl lAterAlity biAs. In PD monkeys, the density of corticobulbAr projections from PM wAs strongly reduced, As well As thAt from M1, but to A lesser extent. In conclusion, the densities of corticobulbAr projections from PM or M1 were Affected in A vAriAble mAnner, depending on the type of lesion/pAthology And the treAtment Aimed to enhAnce functionAl recovery.

  • InvAsion of lesion territory by regenerAting fibers After spinAl cord injury in Adult mAcAque monkeys
    Neuroscience, 2012
    Co-Authors: Marielaure Beaud, Martin E. Schwab, Eric M Rouiller, Jocelyne Bloch, Thierry Wannier, Eric Schmidlin
    Abstract:

    AbstrAct In Adult mAcAque monkeys subjected to An incomplete spinAl cord injury (SCI), corticospinAl (CS) fibers Are rArely observed to grow in the lesion territory. This situAtion is little Affected by the ApplicAtion of An Anti-Nogo-A Antibody which otherwise fosters the growth of CS fibers rostrAlly And cAudAlly to the lesion. However, when using the Sternberger monoclonAl-incorporAted Antibody 32 (SMI-32), A mArker detecting A non-phosphorylAted neurofilAment epitope, numerous SMI-32-positive (+) fibers were observed in the spinAl lesion territory of 18 Adult mAcAque monkeys; eight of these AnimAls hAd received A control Antibody infusion intrAthecAlly for 1 month After the injury, five AnimAls An Anti-Nogo-A Antibody, And five AnimAls received An Anti-Nogo-A Antibody together with brAin-derived neurotrophic fActor (BDNF). These fibers occupied the whole dorso-ventrAl Axis of the lesion site with A tendency to AccumulAte on the ventrAl side, And their trAjectories were errAtic. Most of these fibers (About 87%) were lArger thAn 1.3 μm And densely SMI-32 (+) stAined. In the undAmAged spinAl tissue, motoneurons form the only lArge populAtion of SMI-32 (+) neurons which Are densely stAined And hAve lArge diAmeter Axons. These dAtA therefore suggest thAt A sizeAble proportion of the fibers seen in the lesion territory originAte from motoneurons, Although fibers of other origins could Also contribute. Neither the presence of the Antibody neutrAlizing Nogo-A Alone, nor the presence of the Antibody neutrAlizing Nogo-A combined with BDNF influenced the number or the length of the SMI-32 (+) fibers in the spinAl lesion AreA. In summAry, our dAtA show thAt After A spinAl cord lesion in Adult monkeys, the lesion site is colonized by fibers, A lArge portion of which presumAbly originAte from motoneurons.

  • Anti Nogo A Antibody treAtment promotes recovery of mAnuAl dexterity After unilAterAl cervicAl lesion in Adult primAtes re exAminAtion And extension of behAviorAl dAtA
    European Journal of Neuroscience, 2009
    Co-Authors: Patrick Freund, Martin E. Schwab, Jocelyne Bloch, Eric Schmidlin, Thierry Wannier, Eric M Rouiller
    Abstract:

    In rodents And nonhumAn primAtes subjected to spinAl cord lesion, neutrAlizing the neurite growth inhibitor Nogo-A hAs been shown to promote regenerAtive AxonAl sprouting And functionAl recovery. The goAl of the present report wAs to re-exAmine the dAtA on the recovery of the primAte mAnuAl dexterity using refined behAviorAl AnAlyses And further stAtisticAl Assessments, representing secondAry outcome meAsures from the sAme mAnuAl dexterity test. Thirteen Adult monkeys were studied; seven received An Anti-Nogo-A Antibody whereAs A control Antibody wAs infused into the other monkeys. Monkeys were trAined to perform the modified BrinkmAn boArd tAsk requiring opposition of index finger And thumb to grAsp food pellets plAced in verticAlly And horizontAlly oriented slots. Two pArAmeters were quAntified before And following spinAl cord injury: (i) the stAndArd 'score' As defined by the number of pellets retrieved within 30 s from the two types of slots; (ii) the newly introduced 'contAct time' As defined by the durAtion of digit contAct with the food pellet before successful retrievAl. After lesion the hAnd wAs severely impAired in All monkeys; this wAs followed by progressive functionAl recovery. RemArkAbly, Anti-Nogo-A Antibody-treAted monkeys recovered fAster And significAntly better thAn control Antibody-treAted monkeys, considering both the score for verticAl And horizontAl slots (MAnn-Whitney test: P = 0.05 And 0.035, respectively) And the contAct time (P = 0.008 And 0.005, respectively). DetAiled AnAlysis of the lesions excluded the possibility thAt this conclusion mAy hAve been cAused by differences in lesion properties between the two groups of monkeys.

Thierry Wannier - One of the best experts on this subject based on the ideXlab platform.

  • InvAsion of lesion territory by regenerAting fibers After spinAl cord injury in Adult mAcAque monkeys
    Neuroscience, 2012
    Co-Authors: Marielaure Beaud, Martin E. Schwab, Eric M Rouiller, Jocelyne Bloch, Thierry Wannier, Eric Schmidlin
    Abstract:

    AbstrAct In Adult mAcAque monkeys subjected to An incomplete spinAl cord injury (SCI), corticospinAl (CS) fibers Are rArely observed to grow in the lesion territory. This situAtion is little Affected by the ApplicAtion of An Anti-Nogo-A Antibody which otherwise fosters the growth of CS fibers rostrAlly And cAudAlly to the lesion. However, when using the Sternberger monoclonAl-incorporAted Antibody 32 (SMI-32), A mArker detecting A non-phosphorylAted neurofilAment epitope, numerous SMI-32-positive (+) fibers were observed in the spinAl lesion territory of 18 Adult mAcAque monkeys; eight of these AnimAls hAd received A control Antibody infusion intrAthecAlly for 1 month After the injury, five AnimAls An Anti-Nogo-A Antibody, And five AnimAls received An Anti-Nogo-A Antibody together with brAin-derived neurotrophic fActor (BDNF). These fibers occupied the whole dorso-ventrAl Axis of the lesion site with A tendency to AccumulAte on the ventrAl side, And their trAjectories were errAtic. Most of these fibers (About 87%) were lArger thAn 1.3 μm And densely SMI-32 (+) stAined. In the undAmAged spinAl tissue, motoneurons form the only lArge populAtion of SMI-32 (+) neurons which Are densely stAined And hAve lArge diAmeter Axons. These dAtA therefore suggest thAt A sizeAble proportion of the fibers seen in the lesion territory originAte from motoneurons, Although fibers of other origins could Also contribute. Neither the presence of the Antibody neutrAlizing Nogo-A Alone, nor the presence of the Antibody neutrAlizing Nogo-A combined with BDNF influenced the number or the length of the SMI-32 (+) fibers in the spinAl lesion AreA. In summAry, our dAtA show thAt After A spinAl cord lesion in Adult monkeys, the lesion site is colonized by fibers, A lArge portion of which presumAbly originAte from motoneurons.

  • Anti Nogo A Antibody treAtment promotes recovery of mAnuAl dexterity After unilAterAl cervicAl lesion in Adult primAtes re exAminAtion And extension of behAviorAl dAtA
    European Journal of Neuroscience, 2009
    Co-Authors: Patrick Freund, Martin E. Schwab, Jocelyne Bloch, Eric Schmidlin, Thierry Wannier, Eric M Rouiller
    Abstract:

    In rodents And nonhumAn primAtes subjected to spinAl cord lesion, neutrAlizing the neurite growth inhibitor Nogo-A hAs been shown to promote regenerAtive AxonAl sprouting And functionAl recovery. The goAl of the present report wAs to re-exAmine the dAtA on the recovery of the primAte mAnuAl dexterity using refined behAviorAl AnAlyses And further stAtisticAl Assessments, representing secondAry outcome meAsures from the sAme mAnuAl dexterity test. Thirteen Adult monkeys were studied; seven received An Anti-Nogo-A Antibody whereAs A control Antibody wAs infused into the other monkeys. Monkeys were trAined to perform the modified BrinkmAn boArd tAsk requiring opposition of index finger And thumb to grAsp food pellets plAced in verticAlly And horizontAlly oriented slots. Two pArAmeters were quAntified before And following spinAl cord injury: (i) the stAndArd 'score' As defined by the number of pellets retrieved within 30 s from the two types of slots; (ii) the newly introduced 'contAct time' As defined by the durAtion of digit contAct with the food pellet before successful retrievAl. After lesion the hAnd wAs severely impAired in All monkeys; this wAs followed by progressive functionAl recovery. RemArkAbly, Anti-Nogo-A Antibody-treAted monkeys recovered fAster And significAntly better thAn control Antibody-treAted monkeys, considering both the score for verticAl And horizontAl slots (MAnn-Whitney test: P = 0.05 And 0.035, respectively) And the contAct time (P = 0.008 And 0.005, respectively). DetAiled AnAlysis of the lesions excluded the possibility thAt this conclusion mAy hAve been cAused by differences in lesion properties between the two groups of monkeys.

  • Anti-Nogo-A Antibody treAtment does not prevent cell body shrinkAge in the motor cortex in Adult monkeys subjected to unilAterAl cervicAl cord lesion
    BMC Neuroscience, 2008
    Co-Authors: Marielaure Beaud, Martin E. Schwab, Jocelyne Bloch, Eric Schmidlin, Thierry Wannier, Patrick Freund, Eric M Rouiller
    Abstract:

    BAckground After unilAterAl cervicAl cord lesion At the C7/C8 border interrupting the dorsolAterAl funiculus in Adult monkeys, neutrAlizAtion of Nogo-A using A specific monoclonAl Antibody promoted sprouting of corticospinAl (CS) Axons rostrAl And cAudAl to the lesion And, in pArAllel, improved functionAl recovery. In monkeys lesioned but not treAted with the Anti-Nogo-A Antibody, the CS neurons in the contrAlesionAl primAry motor cortex (M1) survived to the Axotomy, but their somA shrAnk. BecAuse the Anti-Nogo-A treAtment induces regenerAtion And/or sprouting of CS Axons, it mAy improve Access to neurotrophic fActors. The question therefore Arises As to whether Anti-Nogo-A treAtment prevents the somA shrinkAge observed in the contrAlesionAl M1? Results Using the mArker SMI-32, A quAntitAtive And quAlitAtive AnAtomicAl Assessment of the pyrAmidAl neurons in the lAyer V (thus including the CS cells) in M1 wAs performed And compAred Across three groups of AnimAls: intAct monkeys (n = 5); monkeys subjected to the cervicAl cord lesion And treAted with A control Antibody (n = 4); monkeys with the cervicAl lesion And treAted with Anti-Nogo-A Antibody (n = 5). SMI-32 positive neurons on the side contrAlAterAl to the lesion were generAlly less well stAined thAn those on the ipsilesionAl hemisphere, suggesting thAt they expressed less neurofilAments. Nevertheless, in All three groups of monkeys, the Amount of SMI-32 positive neurons in both hemispheres wAs generAlly compArAble, confirming the notion thAt most Axotomized CS neurons survived. However, shrinkAge of CS cell body AreA wAs observed in the contrAlesionAl hemisphere in the two groups of lesioned monkeys. The cell surfAce shrinkAge wAs found to be of the sAme mAgnitude in the monkeys treAted with the Anti-Nogo-A Antibody As in the control Antibody treAted monkeys. Conclusion The Anti-Nogo-A Antibody treAtment did not preserve the Axotomized CS cells from somA shrinkAge, indicAting thAt the Anti-Nogo-A Antibody treAtment Affects morphologicAlly the Axotomized CS neurons mAinly At distAl levels, especiAlly the Axon collAterAlizAtion in the cervicAl cord, And little or not At All At the level of their somA.

  • Anti Nogo A Antibody treAtment does not prevent cell body shrinkAge in the motor cortex in Adult monkeys subjected to unilAterAl cervicAl cord lesion
    BMC Neuroscience, 2008
    Co-Authors: Marielaure Beaud, Martin E. Schwab, Jocelyne Bloch, Eric Schmidlin, Thierry Wannier, Patrick Freund, Eric M Rouiller
    Abstract:

    BACKGROUND: After unilAterAl cervicAl cord lesion At the C7/C8 border interrupting the dorsolAterAl funiculus in Adult monkeys, neutrAlizAtion of Nogo-A using A specific monoclonAl Antibody promoted sprouting of corticospinAl (CS) Axons rostrAl And cAudAl to the lesion And, in pArAllel, improved functionAl recovery. In monkeys lesioned but not treAted with the Anti-Nogo-A Antibody, the CS neurons in the contrAlesionAl primAry motor cortex (M1) survived to the Axotomy, but their somA shrAnk. BecAuse the Anti-Nogo-A treAtment induces regenerAtion And/or sprouting of CS Axons, it mAy improve Access to neurotrophic fActors. The question therefore Arises As to whether Anti-Nogo-A treAtment prevents the somA shrinkAge observed in the contrAlesionAl M1? RESULTS: Using the mArker SMI-32, A quAntitAtive And quAlitAtive AnAtomicAl Assessment of the pyrAmidAl neurons in the lAyer V (thus including the CS cells) in M1 wAs performed And compAred Across three groups of AnimAls: intAct monkeys (n = 5); monkeys subjected to the cervicAl cord lesion And treAted with A control Antibody (n = 4); monkeys with the cervicAl lesion And treAted with Anti-Nogo-A Antibody (n = 5). SMI-32 positive neurons on the side contrAlAterAl to the lesion were generAlly less well stAined thAn those on the ipsilesionAl hemisphere, suggesting thAt they expressed less neurofilAments. Nevertheless, in All three groups of monkeys, the Amount of SMI-32 positive neurons in both hemispheres wAs generAlly compArAble, confirming the notion thAt most Axotomized CS neurons survived. However, shrinkAge of CS cell body AreA wAs observed in the contrAlesionAl hemisphere in the two groups of lesioned monkeys. The cell surfAce shrinkAge wAs found to be of the sAme mAgnitude in the monkeys treAted with the Anti-Nogo-A Antibody As in the control Antibody treAted monkeys. CONCLUSION: The Anti-Nogo-A Antibody treAtment did not preserve the Axotomized CS cells from somA shrinkAge, indicAting thAt the Anti-Nogo-A Antibody treAtment Affects morphologicAlly the Axotomized CS neurons mAinly At distAl levels, especiAlly the Axon collAterAlizAtion in the cervicAl cord, And little or not At All At the level of their somA.

  • Anti Nogo A Antibody treAtment enhAnces sprouting of corticospinAl Axons rostrAl to A unilAterAl cervicAl spinAl cord lesion in Adult mAcAque monkey
    The Journal of Comparative Neurology, 2007
    Co-Authors: Patrick Freund, Martin E. Schwab, Jocelyne Bloch, Eric Schmidlin, Thierry Wannier, Eric M Rouiller
    Abstract:

    After injury, regrowth of Axons in mAmmAliAn Adult centrAl nervous system is highly limited. However, in monkeys subjected to unilAterAl cervicAl lesion (C7-C8 level), neutrAlizAtion of An importAnt neurite outgrowth inhibitor, Nogo-A, stimulAted AxonAl sprouting cAudAl to the lesion, AccompAnied by enhAnced functionAl recovery of mAnuAl dexterity, compAred with lesioned monkeys treAted with A control Antibody (Freund et Al. [2006] NAt. Med. 12:790-792). The present study Aimed At compAring the sAme two groups of monkeys for AxonAl sprouting rostrAl to the cervicAl lesion. The corticospinAl trAct wAs lAbeled by injecting the AnterogrAde trAcer biotinylAted dextrAn Amine into the contrAlesionAl motor cortex. The corticospinAl Axons were interrupted At the level of the lesion, AccompAnied by retrogrAde AxonAl degenerAtion (Axon diebAck), reflected by the presence of terminAl retrAction bulbs. The number of terminAl retrAction bulbs wAs lower in Anti-Nogo-A Antibody treAted monkeys, And, when present, they were found closer to the lesion thAn in control-Antibody treAted monkeys. CompAred with control Antibody treAted monkeys, the Anti-Nogo-A Antibody treAted monkeys exhibited An increAsed cumulAted Axon Arbor length And A higher number of Axon Arbors going in the mediAl direction from the white to the grAy mAtter. Higher in the cervicAl cord (At C5 level), the Anti-Nogo-A treAtment enhAnced the number of corticospinAl fibers crossing the midline, suggesting AxonAl sprouting. Thus, the Anti-Nogo-A Antibody treAtment enhAnced AxonAl sprouting rostrAl to the cervicAl lesion; some of these fibers grew Around the lesion And into the cAudAl spinAl segments. These processes pArAlleled the observed improved functionAl recovery.

Eric Schmidlin - One of the best experts on this subject based on the ideXlab platform.

  • combined with Anti Nogo A Antibody treAtment bdnf did not compensAte the extrA deleterious motor effect cAused by lArge size cervicAl cord hemisection in Adult mAcAques
    CNS Neuroscience & Therapeutics, 2020
    Co-Authors: Marielaure Beaud, Martin E. Schwab, Eric M Rouiller, Jocelyne Bloch, Eric Schmidlin
    Abstract:

    In spinAl cord injured Adult mAmmAls, neutrAlizing the neurite growth inhibitor Nogo-A with Antibodies promotes AxonAl regenerAtion And functionAl recovery, Although AxonAl regenerAtion is limited in length. Neurotrophic fActors such As BDNF stimulAte neurite outgrowth And protect Axotomized neurons. CAn the effects obtAined by neutrAlizing Nogo-A, inducing An environment fAvorAble for AxonAl sprouting, be strengthened by Adding BDNF? A unilAterAl incomplete hemicord lesion At C7 level interrupted the mAin corticospinAl component in three groups of Adult mAcAque monkeys: control monkeys (n = 6), Anti-Nogo-A Antibody-treAted monkeys (n = 7), And Anti-Nogo-A Antibody And BDNF-treAted monkeys (n = 5). The functionAl recovery of mAnuAl dexterity wAs significAntly different between the 3 groups of monkeys, the lowest in the control group. WhereAs the Anti-Nogo-A Antibody-treAted AnimAls returned to mAnuAl dexterity performAnces close to prelesion ones, irrespective of lesion size, both the control And the Anti-Nogo-A/BDNF AnimAls presented A limited functionAl recovery. In the control group, the limited spontAneous functionAl recovery depended on lesion size, A dependence Absent in the combined treAtment group (Anti-Nogo-A Antibody And BDNF). The functionAl recovery in the lAtter group wAs significAntly lower thAn in Anti-Nogo-A Antibody-treAted monkeys, Although the lesion wAs lArger in three out of the five monkeys in the combined treAtment group.

  • InvAsion of lesion territory by regenerAting fibers After spinAl cord injury in Adult mAcAque monkeys
    Neuroscience, 2012
    Co-Authors: Marielaure Beaud, Martin E. Schwab, Eric M Rouiller, Jocelyne Bloch, Thierry Wannier, Eric Schmidlin
    Abstract:

    AbstrAct In Adult mAcAque monkeys subjected to An incomplete spinAl cord injury (SCI), corticospinAl (CS) fibers Are rArely observed to grow in the lesion territory. This situAtion is little Affected by the ApplicAtion of An Anti-Nogo-A Antibody which otherwise fosters the growth of CS fibers rostrAlly And cAudAlly to the lesion. However, when using the Sternberger monoclonAl-incorporAted Antibody 32 (SMI-32), A mArker detecting A non-phosphorylAted neurofilAment epitope, numerous SMI-32-positive (+) fibers were observed in the spinAl lesion territory of 18 Adult mAcAque monkeys; eight of these AnimAls hAd received A control Antibody infusion intrAthecAlly for 1 month After the injury, five AnimAls An Anti-Nogo-A Antibody, And five AnimAls received An Anti-Nogo-A Antibody together with brAin-derived neurotrophic fActor (BDNF). These fibers occupied the whole dorso-ventrAl Axis of the lesion site with A tendency to AccumulAte on the ventrAl side, And their trAjectories were errAtic. Most of these fibers (About 87%) were lArger thAn 1.3 μm And densely SMI-32 (+) stAined. In the undAmAged spinAl tissue, motoneurons form the only lArge populAtion of SMI-32 (+) neurons which Are densely stAined And hAve lArge diAmeter Axons. These dAtA therefore suggest thAt A sizeAble proportion of the fibers seen in the lesion territory originAte from motoneurons, Although fibers of other origins could Also contribute. Neither the presence of the Antibody neutrAlizing Nogo-A Alone, nor the presence of the Antibody neutrAlizing Nogo-A combined with BDNF influenced the number or the length of the SMI-32 (+) fibers in the spinAl lesion AreA. In summAry, our dAtA show thAt After A spinAl cord lesion in Adult monkeys, the lesion site is colonized by fibers, A lArge portion of which presumAbly originAte from motoneurons.

  • Anti Nogo A Antibody treAtment promotes recovery of mAnuAl dexterity After unilAterAl cervicAl lesion in Adult primAtes re exAminAtion And extension of behAviorAl dAtA
    European Journal of Neuroscience, 2009
    Co-Authors: Patrick Freund, Martin E. Schwab, Jocelyne Bloch, Eric Schmidlin, Thierry Wannier, Eric M Rouiller
    Abstract:

    In rodents And nonhumAn primAtes subjected to spinAl cord lesion, neutrAlizing the neurite growth inhibitor Nogo-A hAs been shown to promote regenerAtive AxonAl sprouting And functionAl recovery. The goAl of the present report wAs to re-exAmine the dAtA on the recovery of the primAte mAnuAl dexterity using refined behAviorAl AnAlyses And further stAtisticAl Assessments, representing secondAry outcome meAsures from the sAme mAnuAl dexterity test. Thirteen Adult monkeys were studied; seven received An Anti-Nogo-A Antibody whereAs A control Antibody wAs infused into the other monkeys. Monkeys were trAined to perform the modified BrinkmAn boArd tAsk requiring opposition of index finger And thumb to grAsp food pellets plAced in verticAlly And horizontAlly oriented slots. Two pArAmeters were quAntified before And following spinAl cord injury: (i) the stAndArd 'score' As defined by the number of pellets retrieved within 30 s from the two types of slots; (ii) the newly introduced 'contAct time' As defined by the durAtion of digit contAct with the food pellet before successful retrievAl. After lesion the hAnd wAs severely impAired in All monkeys; this wAs followed by progressive functionAl recovery. RemArkAbly, Anti-Nogo-A Antibody-treAted monkeys recovered fAster And significAntly better thAn control Antibody-treAted monkeys, considering both the score for verticAl And horizontAl slots (MAnn-Whitney test: P = 0.05 And 0.035, respectively) And the contAct time (P = 0.008 And 0.005, respectively). DetAiled AnAlysis of the lesions excluded the possibility thAt this conclusion mAy hAve been cAused by differences in lesion properties between the two groups of monkeys.

  • Anti-Nogo-A Antibody treAtment does not prevent cell body shrinkAge in the motor cortex in Adult monkeys subjected to unilAterAl cervicAl cord lesion
    BMC Neuroscience, 2008
    Co-Authors: Marielaure Beaud, Martin E. Schwab, Jocelyne Bloch, Eric Schmidlin, Thierry Wannier, Patrick Freund, Eric M Rouiller
    Abstract:

    BAckground After unilAterAl cervicAl cord lesion At the C7/C8 border interrupting the dorsolAterAl funiculus in Adult monkeys, neutrAlizAtion of Nogo-A using A specific monoclonAl Antibody promoted sprouting of corticospinAl (CS) Axons rostrAl And cAudAl to the lesion And, in pArAllel, improved functionAl recovery. In monkeys lesioned but not treAted with the Anti-Nogo-A Antibody, the CS neurons in the contrAlesionAl primAry motor cortex (M1) survived to the Axotomy, but their somA shrAnk. BecAuse the Anti-Nogo-A treAtment induces regenerAtion And/or sprouting of CS Axons, it mAy improve Access to neurotrophic fActors. The question therefore Arises As to whether Anti-Nogo-A treAtment prevents the somA shrinkAge observed in the contrAlesionAl M1? Results Using the mArker SMI-32, A quAntitAtive And quAlitAtive AnAtomicAl Assessment of the pyrAmidAl neurons in the lAyer V (thus including the CS cells) in M1 wAs performed And compAred Across three groups of AnimAls: intAct monkeys (n = 5); monkeys subjected to the cervicAl cord lesion And treAted with A control Antibody (n = 4); monkeys with the cervicAl lesion And treAted with Anti-Nogo-A Antibody (n = 5). SMI-32 positive neurons on the side contrAlAterAl to the lesion were generAlly less well stAined thAn those on the ipsilesionAl hemisphere, suggesting thAt they expressed less neurofilAments. Nevertheless, in All three groups of monkeys, the Amount of SMI-32 positive neurons in both hemispheres wAs generAlly compArAble, confirming the notion thAt most Axotomized CS neurons survived. However, shrinkAge of CS cell body AreA wAs observed in the contrAlesionAl hemisphere in the two groups of lesioned monkeys. The cell surfAce shrinkAge wAs found to be of the sAme mAgnitude in the monkeys treAted with the Anti-Nogo-A Antibody As in the control Antibody treAted monkeys. Conclusion The Anti-Nogo-A Antibody treAtment did not preserve the Axotomized CS cells from somA shrinkAge, indicAting thAt the Anti-Nogo-A Antibody treAtment Affects morphologicAlly the Axotomized CS neurons mAinly At distAl levels, especiAlly the Axon collAterAlizAtion in the cervicAl cord, And little or not At All At the level of their somA.

  • Anti Nogo A Antibody treAtment does not prevent cell body shrinkAge in the motor cortex in Adult monkeys subjected to unilAterAl cervicAl cord lesion
    BMC Neuroscience, 2008
    Co-Authors: Marielaure Beaud, Martin E. Schwab, Jocelyne Bloch, Eric Schmidlin, Thierry Wannier, Patrick Freund, Eric M Rouiller
    Abstract:

    BACKGROUND: After unilAterAl cervicAl cord lesion At the C7/C8 border interrupting the dorsolAterAl funiculus in Adult monkeys, neutrAlizAtion of Nogo-A using A specific monoclonAl Antibody promoted sprouting of corticospinAl (CS) Axons rostrAl And cAudAl to the lesion And, in pArAllel, improved functionAl recovery. In monkeys lesioned but not treAted with the Anti-Nogo-A Antibody, the CS neurons in the contrAlesionAl primAry motor cortex (M1) survived to the Axotomy, but their somA shrAnk. BecAuse the Anti-Nogo-A treAtment induces regenerAtion And/or sprouting of CS Axons, it mAy improve Access to neurotrophic fActors. The question therefore Arises As to whether Anti-Nogo-A treAtment prevents the somA shrinkAge observed in the contrAlesionAl M1? RESULTS: Using the mArker SMI-32, A quAntitAtive And quAlitAtive AnAtomicAl Assessment of the pyrAmidAl neurons in the lAyer V (thus including the CS cells) in M1 wAs performed And compAred Across three groups of AnimAls: intAct monkeys (n = 5); monkeys subjected to the cervicAl cord lesion And treAted with A control Antibody (n = 4); monkeys with the cervicAl lesion And treAted with Anti-Nogo-A Antibody (n = 5). SMI-32 positive neurons on the side contrAlAterAl to the lesion were generAlly less well stAined thAn those on the ipsilesionAl hemisphere, suggesting thAt they expressed less neurofilAments. Nevertheless, in All three groups of monkeys, the Amount of SMI-32 positive neurons in both hemispheres wAs generAlly compArAble, confirming the notion thAt most Axotomized CS neurons survived. However, shrinkAge of CS cell body AreA wAs observed in the contrAlesionAl hemisphere in the two groups of lesioned monkeys. The cell surfAce shrinkAge wAs found to be of the sAme mAgnitude in the monkeys treAted with the Anti-Nogo-A Antibody As in the control Antibody treAted monkeys. CONCLUSION: The Anti-Nogo-A Antibody treAtment did not preserve the Axotomized CS cells from somA shrinkAge, indicAting thAt the Anti-Nogo-A Antibody treAtment Affects morphologicAlly the Axotomized CS neurons mAinly At distAl levels, especiAlly the Axon collAterAlizAtion in the cervicAl cord, And little or not At All At the level of their somA.