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439 results on '"Fischer, Itzhak"'

59. Either BDNF or NT-3 only neurotrophin producing grafts promote locomotor recovery in untrained spinalized cats

Author

Ollivier-Lanvin, Karen, Fischer, Itzhak, Tom, Veronica, Houlé, John D., and Lemay, Michel A.

Subjects
Time Factors, Brain-Derived Neurotrophic Factor, Recovery of Function, Fibroblasts, Article, Biomechanical Phenomena, Disease Models, Animal, Neurotrophin 3, Transduction, Genetic, Cats, Exercise Test, Animals, Female, Locomotion, Spinal Cord Injuries
Abstract

Background. Transplants of cellular grafts expressing a combination of 2 neurotrophic factors, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) have been shown to promote and enhance locomotor recovery in untrained spinalized cats. Based on the time course of recovery and the absence of axonal growth through the transplants, we hypothesized that recovery was due to neurotrophin-mediated plasticity within the existing locomotor circuitry of the lumbar cord. Since BDNF and NT-3 have different effects on axonal sprouting and synaptic connectivity/strengthening, it becomes important to ascertain the contribution of each individual neurotrophins to recovery. Objective. We studied whether BDNF or NT-3 only producing cellular grafts would be equally effective at restoring locomotion in untrained spinal cats. Methods. Rat fibroblasts secreting one of the 2 neurotrophins were grafted into the T12 spinal transection site of adult cats. Four cats in each group (BDNF alone or NT-3 alone) were evaluated. Locomotor recovery was tested on a treadmill at 3 and 5 weeks post-transection/grafting. Results. Animals in both groups were capable of plantar weight-bearing stepping at speed up to 0.8 m/s as early as 3 weeks and locomotor capabilities were similar at 3 and 5 weeks for both types of graft. Conclusions. Even without locomotor training, either BDNF or NT-3 only producing grafts promote locomotor recovery in complete spinal animals. More clinically applicable delivery methods need to be developed.

Published
2014

69. Improving the therapeutic efficacy of neural progenitor cell transplantation following spinal cord injury.

Author

Lane, Michael A., Lepore, Angelo C., and Fischer, Itzhak

Abstract

Introduction: There have been a wide range of preclinical studies testing cellular therapies to repair the injured spinal cord, yet they remain a challenge to translate because of inconsistencies in efficacy, limited number of patients with acute/subacute SCI and the high costs of clinical trials. Area covered: This paper focusses on the therapeutic potential of neural precursor cells (NPCs) because they can provide the cellular components capable of promoting repair and enhancing functional improvement following spinal cord injury (SCI). The authors discuss the challenges of NPC transplantation with respect to different populations of NPCs of glial and neuronal lineages, the timing of treatment relative to acute and chronic injury, and the progress in ongoing clinical trials. Expert commentary: Preclinical research will continue to elucidate mechanisms of recovery associated with NPC transplants, including increasing the partnership with related fields such as spinal atrophies and multiple sclerosis. The clinical trials landscape will grow and include both acute and chronic SCI with increased partnership and strengthened communication between biotechnology, government and academia. There will also be growing effort to develop better biomarkers, imaging and outcome measures for detailed assessment of neurological function and measures of quality of life. [ABSTRACT FROM PUBLISHER]

Published
2017
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75. Acute administration of AMPA/Kainate blocker combined with delayed transplantation of neural precursors improves lower urinary tract function in spinal injured rats

Author

Mitsui, Takahiko, Neuhuber, Birgit, Fischer, Itzhak, Mitsui, Takahiko, Neuhuber, Birgit, and Fischer, Itzhak

Abstract

To evaluate bladder function recovery after spinal cord injury (SCI) in response to a combination treatment of an acutely administered AMPA/kainate receptor antagonist and delayed transplantation of neuronal precursors. Female rats received a contusion injury at T8/9. The AMPA/kainate receptor antagonist NBQX was directly administered into the lesion site immediately after injury. Nine days post-injury, NRP/GRP were delivered into the lesion site. Controls received NRP/GRP grafts only or no treatment (OP-Controls). Animals underwent bladder function testing during the course of the experiment and at the endpoint. Motor function was evaluated as well. After sacrifice, histological analysis of lesion site and lumbosacral spinal cord regions was performed. Rats receiving the combined treatment (NBQX&NRP/GRP) had voided volumes/micturition resembling that of normal animals and showed greater improvement of urodynamic parameters, compared to NRP/GRP alone or OP-Controls. Similarly, NBQX&NRP/GRP induced more spouting, regeneration or sparing of descending projections to the lumbosacral cord. The density of primary afferent projections at the lumbosacral spinal cord in rats with combined treatments was similar to that of NRP/GRP alone with decreased sprouting of primary afferents in lumbosacral cord, compared to OP-Control. Immunohistochemical evaluation revealed that the combined treatment reduced the size of the lesion to a greater extent than NRP/GRP alone or OP-Controls. NRP/GRP with and without NBQX produced a significant recovery of hindlimb compared to OP-Controls. In conclusion, transplants of NRP/GRP combined with NBQX promote recovery of micturition function following spinal cord injury, likely through increased neuroprotection.

Published
2011

81. A pilot study of poly(N-isopropylacrylamide)-g-polyethylene glycol and poly(N-isopropylacrylamide)-g-methylcellulose branched copolymers as injectable scaffolds for local delivery of neurotrophins and cellular transplants into the injured spinal cord

Author

Conova, Lauren, primary, Vernengo, Jennifer, additional, Jin, Ying, additional, Himes, B. Timothy, additional, Neuhuber, Birgit, additional, Fischer, Itzhak, additional, and Lowman, Anthony, additional

Published
2011
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