The Experts below are selected from a list of 39447 Experts worldwide ranked by ideXlab platform
Wolfram Tetzlaff - One of the best experts on this subject based on the ideXlab platform.
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combination of olfactory ensheathing cells with local versus systemic camp treatment after a cervical rubrospinal tract injury
Journal of Neuroscience Research, 2010Co-Authors: Frederic Bretzner, Miranda W Richter, Jane A Roskams, Jason R Plemel, Jie Liu, Wolfram TetzlaffAbstract:The failure of CNS axons to regenerate following traumatic injury is due in part to a growth-inhibitory environment in CNS as well as a weak intrinsic neuronal growth response. Olfactory ensheathing cell (OECs) transplants have been reported to create a favorable environment promoting axonal regeneration, remyelination, and functional recovery after spinal cord injury. However, in our previous experiments, OEC transplants failed to promote regeneration of rubrospinal axons through and beyond the site of a dorsolateral funiculus crush in rats. Rubrospinal neurons undergo massive cell atrophy and limited expression of regeneration-associated genes after axotomy. Using the same injury model, we Tested the hypothesis that treatment of the red nucleus with cAMP, known to stimulate the intrinsic growth response in other neurons, will promote rubrospinal regeneration in combination with OEC transplants. In addition, we assessed a systemic increase of cAMP using the phosphodiesterase inhibitor rolipram. OECs prevented cavity formation, attenuated astrocytic hypertrophy and the retraction of the axotomized rubrospinal axons, and tended to reduce the overall lesion size. OEC transplantation lowered the thresholds for thermal sensitivity of both forepaws. None of our treatments, alone or in combination, promoted rubrospinal regeneration through the lesion site. However, the systemic elevation of cAMP with rolipram resulted in greater numbers of OECs and axonal density within the graft and improved motor performance in a Cylinder Test in conjunction with enhanced rubrospinal branching and attenuated astrocytic hypertrophy. © 2010 Wiley-Liss, Inc.
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undesired effects of a combinatorial treatment for spinal cord injury transplantation of olfactory ensheathing cells and bdnf infusion to the red nucleus
European Journal of Neuroscience, 2008Co-Authors: Frederic Bretzner, Jane A Roskams, Jie Liu, Erin Currie, Wolfram TetzlaffAbstract:Transplantations of olfactory ensheathing cells (OECs) have been reported to promote axonal regeneration and functional recovery after spinal cord injury, but have demonstrated limited growth promotion of rat rubrospinal axons after a cervical dorsolateral funiculus crush. Rubrospinal neurons undergo massive atrophy after cervical axotomy and show only transient expression of regeneration-associated genes. Cell body treatment with brain-derived neurotrophic factor (BDNF) prevents this atrophy, stimulates regeneration-associated gene expression and promotes regeneration of rubrospinal axons into peripheral nerve transplants. Here, we hypothesized that the failure of rubrospinal axons to regenerate through a bridge of OEC transplants was due to this weak intrinsic cell body response. Hence, we combined BDNF treatment of rubrospinal neurons with transplantation of highly enriched OECs derived from the nasal mucosa and assessed axonal regeneration as well as behavioral changes after a cervical dorsolateral funiculus crush. Each treatment alone as well as their combination prevented the dieback of the rubrospinal axons, but none of them promoted rubrospinal regeneration beyond the lesion/transplantation site. Motor performance in a food-pellet reaching Test and forelimb usage during vertical exploration (Cylinder Test) were more impaired after combining transplantation of OECs with BDNF treatment. This impaired motor performance correlated with lowered sensory thresholds in animals receiving the combinatorial therapy - which were not seen with each treatment alone. Only this combinatorial treatment group showed enhanced sprouting of calcitonin gene-related peptide-positive axons rostral to the lesion site. Hence, some combinatorial treatments, such as OECs with BDNF, may have undesired effects in the injured spinal cord.
Angela M Cenci - One of the best experts on this subject based on the ideXlab platform.
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pridopidine induces functional neurorestoration via the sigma 1 receptor in a mouse model of parkinson s disease
Neurotherapeutics, 2019Co-Authors: Veronica Francardo, Michal Geva, Francesco Bez, Quentin Denis, Lilach Steiner, Michael R Hayden, Angela M CenciAbstract:Pridopidine is a small molecule in clinical development for the treatment of Huntington’s disease. It was recently found to have high binding affinity to the sigma-1 receptor, a chaperone protein involved in cellular defense mechanisms and neuroplasticity. Here, we have evaluated the neuroprotective and neurorestorative effects of pridopidine in a unilateral 6-hydroxydopamine (6-OHDA) lesion model of parkinsonism in mice. By 5 weeks of daily administration, a low dose of pridopidine (0.3 mg/kg) had significantly improved deficits in forelimb use (Cylinder Test, stepping Test) and abolished the ipsilateral rotational bias typical of hemiparkinsonian animals. A higher dose of pridopidine (1 mg/kg) significantly improved only the rotational bias, with a trend towards improvement in forelimb use. The behavioral recovery induced by pridopidine 0.3 mg/kg was accompanied by a significant protection of nigral dopamine cell bodies, an increased dopaminergic fiber density in the striatum, and striatal upregulation of GDNF, BDNF, and phosphorylated ERK1/2. The beneficial effects of pridopidine 0.3 mg/kg were absent in 6-OHDA-lesioned mice lacking the sigma-1 receptor. Pharmacokinetic data confirmed that the effective dose of pridopidine reached brain concentrations sufficient to bind S1R. Our results are the first to show that pridopidine promotes functional neurorestoration in the damaged nigrostriatal system acting via the sigma-1 receptor.
Arthur Giraldiguimaraes - One of the best experts on this subject based on the ideXlab platform.
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does treatment with bone marrow mononuclear cells recover skilled motor function after focal cortical ischemia analysis with a forelimb skilled motor task in rats
Brain Research, 2013Co-Authors: Maria De Fatima Dos Santos Sampaio, Fralini Dos Santos Marcilio, Arthur GiraldiguimaraesAbstract:Abstract Previous studies have shown sensorimotor recovery by treatment with bone marrow mononuclear cells (BMMCs) after focal brain ischemia. However, sensorimotor Tests commonly used are designed to examine motor patterns that do not involve skill or training. We evaluated whether BMMCs treatment was able to recover forelimb skilled movements. Reaching chamber/pellet retrieval (RCPR) task was used, in which animals had to learn to grasp a single food pellet and lead it to its mouth. We also evaluated therapeutic effect of this training on unskilled sensorimotor function. Adult male Wistar rats suffered unilateral cortical ischemia by thermocoagulation in motor and somesthetic primary areas. A day later, they received i.v. injection of 3×10 7 BMMCs or vehicle (saline), forming four experimental groups: BMMCs+RCPR; saline+RCPR; BMMCs and saline. Cylinder and adhesive Tests were applied in all experimental groups, and all behavioral Tests were performed before and along post-ischemic weeks after induction of ischemia. Results from RCPR task showed no significant difference between BMMCs+RCPR and saline+RCPR groups. In Cylinder Test, BMMCs-treated groups showed significant recovery, but no significant effect of RCPR training was observed. In adhesive Test, BMMCs treatment promoted significant recovery. Synergistic effect was found since only together they were able to accelerate recovery. The results showed that BMMCs treatment promoted increased recovery of unsophisticated sensorimotor function, but not of skilled forepaw movements. Thus, BMMCs might not be able to recover all aspects of sensorimotor functions, although further studies are still needed to investigate this treatment in ischemic lesions with different locations and extensions.
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therapeutic window for treatment of cortical ischemia with bone marrow derived cells in rats
Brain Research, 2010Co-Authors: Andreia De Vasconcelos Dos Santos, Juliana Da Costa Reis, Bruno Diaz Paredes, Louise Moraes, Arthur Giraldiguimaraes, Rosalia MendezoteroAbstract:Abstract The beneficial effect of treatment with bone marrow mononuclear cells (BMMCs) was evaluated in different therapeutic windows in a rat model of focal ischemia induced by thermocoagulation of the blood vessels in the left motor, somestesic, and sensorimotor cortices. We also compared the therapeutic benefits between BMMCs and bone marrow-derived mesenchymal stem cells (MSCs). BMMCs and MSCs were obtained from donor rats and injected into the jugular vein after ischemia. BMMCs-treated animals received approximately 3 × 107 cells at post-ischemic days (PIDs) 1, 7, 14, or 30. MSCs-treated animals received approximately 3 × 106 cells at PIDs 1 and 30. Control animals received only the vehicle. The animals were then evaluated for functional sensorimotor recovery weekly with behavioral Tests (Cylinder Test and adhesive Test). Significant recovery of sensorimotor function was only observed in the Cylinder Test in animals treated with BMMCs at PIDs 1 and 7. Similar effects were also observed in the animals treated with MSCs 1 day after ischemia, but not in animals treated with MSCs 30 days after ischemia. Significant decrease in glial scarring did not seem to be a mechanism of action of BMMCs, since treatment with BMMCs did not change the level of expression of GFAP, indicating no significant change in the astrocytic scar in the periphery of the ischemic lesion. These results suggest that BMMCs might be an efficient treatment protocol for stroke only in the acute/subacute phase of the disease, and its efficiency in inducing functional recovery is similar to that of MSCs.
Frederic Bretzner - One of the best experts on this subject based on the ideXlab platform.
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combination of olfactory ensheathing cells with local versus systemic camp treatment after a cervical rubrospinal tract injury
Journal of Neuroscience Research, 2010Co-Authors: Frederic Bretzner, Miranda W Richter, Jane A Roskams, Jason R Plemel, Jie Liu, Wolfram TetzlaffAbstract:The failure of CNS axons to regenerate following traumatic injury is due in part to a growth-inhibitory environment in CNS as well as a weak intrinsic neuronal growth response. Olfactory ensheathing cell (OECs) transplants have been reported to create a favorable environment promoting axonal regeneration, remyelination, and functional recovery after spinal cord injury. However, in our previous experiments, OEC transplants failed to promote regeneration of rubrospinal axons through and beyond the site of a dorsolateral funiculus crush in rats. Rubrospinal neurons undergo massive cell atrophy and limited expression of regeneration-associated genes after axotomy. Using the same injury model, we Tested the hypothesis that treatment of the red nucleus with cAMP, known to stimulate the intrinsic growth response in other neurons, will promote rubrospinal regeneration in combination with OEC transplants. In addition, we assessed a systemic increase of cAMP using the phosphodiesterase inhibitor rolipram. OECs prevented cavity formation, attenuated astrocytic hypertrophy and the retraction of the axotomized rubrospinal axons, and tended to reduce the overall lesion size. OEC transplantation lowered the thresholds for thermal sensitivity of both forepaws. None of our treatments, alone or in combination, promoted rubrospinal regeneration through the lesion site. However, the systemic elevation of cAMP with rolipram resulted in greater numbers of OECs and axonal density within the graft and improved motor performance in a Cylinder Test in conjunction with enhanced rubrospinal branching and attenuated astrocytic hypertrophy. © 2010 Wiley-Liss, Inc.
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undesired effects of a combinatorial treatment for spinal cord injury transplantation of olfactory ensheathing cells and bdnf infusion to the red nucleus
European Journal of Neuroscience, 2008Co-Authors: Frederic Bretzner, Jane A Roskams, Jie Liu, Erin Currie, Wolfram TetzlaffAbstract:Transplantations of olfactory ensheathing cells (OECs) have been reported to promote axonal regeneration and functional recovery after spinal cord injury, but have demonstrated limited growth promotion of rat rubrospinal axons after a cervical dorsolateral funiculus crush. Rubrospinal neurons undergo massive atrophy after cervical axotomy and show only transient expression of regeneration-associated genes. Cell body treatment with brain-derived neurotrophic factor (BDNF) prevents this atrophy, stimulates regeneration-associated gene expression and promotes regeneration of rubrospinal axons into peripheral nerve transplants. Here, we hypothesized that the failure of rubrospinal axons to regenerate through a bridge of OEC transplants was due to this weak intrinsic cell body response. Hence, we combined BDNF treatment of rubrospinal neurons with transplantation of highly enriched OECs derived from the nasal mucosa and assessed axonal regeneration as well as behavioral changes after a cervical dorsolateral funiculus crush. Each treatment alone as well as their combination prevented the dieback of the rubrospinal axons, but none of them promoted rubrospinal regeneration beyond the lesion/transplantation site. Motor performance in a food-pellet reaching Test and forelimb usage during vertical exploration (Cylinder Test) were more impaired after combining transplantation of OECs with BDNF treatment. This impaired motor performance correlated with lowered sensory thresholds in animals receiving the combinatorial therapy - which were not seen with each treatment alone. Only this combinatorial treatment group showed enhanced sprouting of calcitonin gene-related peptide-positive axons rostral to the lesion site. Hence, some combinatorial treatments, such as OECs with BDNF, may have undesired effects in the injured spinal cord.
Sondra T Bland - One of the best experts on this subject based on the ideXlab platform.
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cns plasticity and assessment of forelimb sensorimotor outcome in unilateral rat models of stroke cortical ablation parkinsonism and spinal cord injury
Neuropharmacology, 2000Co-Authors: Timothy J Schallert, Sheila M Fleming, Leigh J Leasure, Jennifer L Tillerson, Sondra T BlandAbstract:We have reviewed a battery of useful Tests for evaluating sensorimotor function and plasticity acutely and chronically in unilateral rat models of central nervous system injury. These Tests include forelimb use for weight shifting during vertical exploration in a cylindrical enclosure, an adhesive removal Test of sensory function, and forelimb placing. These Tests monitor recovery of sensorimotor function independent of the extent of Test experience. Data are presented for four models, including permanent focal ischemia, focal injury to the forelimb area of sensorimotor cortex, dopaminergic neurodegeneration of the nigrostriatal system, and cervical spinal cord injury. The effect of the dendrite growth promoting factor, Osteogenic Protein-1 (OP-1) on outcome following permanent middle cerebral artery (MCA) occlusion was used as an example to illustrate how the Tests can be applied preclinically. OP-1 showed a beneficial effect on limb use asymmetry in the Cylinder Test.
