New strategies in neural repair

Mh, Tuszynski; Jm, Conner; Blesch, Armin; Smith, David Eugene; Merrill, David A.; Hl, Vahlsing

doi:10.1016/s0079-6123(02)38089-0

Cited by 12 publications

(3 citation statements)

References 35 publications

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“…The present results underscore the importance of spared primary afferent neurons after a dorsal root injury. The promotion of the type of terminal sprouting observed in this study, using current regenerative strategies, including the delivery of neurotrophins (Bradbury et al, 2002; Tuszynski et al, 2002) and/or future approaches, may prove to be critical in optimizing any functional compensation and/or recovery of hand function after cervical dorsal root injury.…”

Section: Discussionmentioning

confidence: 82%

Primary afferent terminal sprouting after a cervical dorsal rootlet section in the macaque monkey

Darian‐Smith

2004

J of Comparative Neurology

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We examined the role of primary afferent neurons in the somatosensory cortical "reactivation" that occurs after a localized cervical dorsal root lesion (Darian-Smith and Brown [2000] Nat. Neurosci. 3:476-481). After section of the dorsal rootlets that enervate the macaque's thumb and index finger (segments C6-C8), the cortical representation of these digits was initially silenced but then re-emerged for these same digits over 2-4 postlesion months. Cortical reactivation was accompanied by the emergence of physiologically detectable input from these same digits within dorsal rootlets bordering the lesion site. We investigated whether central axonal sprouting of primary afferents spared by the rhizotomy could mediate this cortical reactivation. The cortical representation of the hand was mapped electrophysiologically 15-25 weeks after the dorsal rootlet section to define this reactivation. Cholera toxin subunit B conjugated to horseradish peroxidase was then injected into the thumb and index finger pads bilaterally to label the central terminals of any neurons that innervated these digits. Primary afferent terminal proliferation was assessed in the spinal dorsal horn and cuneate nucleus at 7 days and 15-25 postlesion weeks. Labeled terminal bouton distributions were reconstructed and the "lesion" and control sides compared within each monkey. Distributions were significantly larger on the side of the lesion in the dorsal horn and cuneate nucleus at 15-25 weeks after the dorsal rootlet section, than those mapped only 7 days postlesion. Our results provide direct evidence for localized sprouting of spared (uninjured) primary afferent terminals in the dorsal horn and cuneate nucleus after a restricted dorsal root injury.

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Section: Discussionmentioning

confidence: 82%

Primary afferent terminal sprouting after a cervical dorsal rootlet section in the macaque monkey

Darian‐Smith

2004

J of Comparative Neurology

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“…It should be noted that everything described is based either on published reports, presentations at meetings that were not under the aegis of confidential information, or selective website searches. Also, other approaches, such as genetically modified cells, 134 which have not yet been tested on SCI subjects, are not discussed, despite their future translational likelihood.…”

Section: Clinical Experiences With Regenerative Sci Cellular Repair Smentioning

confidence: 99%

Cellular transplantation strategies for spinal cord injury and translational neurobiology

Reier

2004

Neurotherapeutics

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Summary: Basic science advances in spinal cord injury and regeneration research have led to a variety of novel experimental therapeutics designed to promote functionally effective axonal regrowth and sprouting. Among these interventions are cell-based approaches involving transplantation of neural and non-neural tissue elements that have potential for restoring damaged neural pathways or reconstructing intraspinal synaptic circuitries by either regeneration or neuronal/glial replacement. Notably, some of these strategies (e.g., grafts of peripheral nerve tissue, olfactory ensheathing glia, activated macrophages, marrow stromal cells, myelin-forming oligodendrocyte precursors or stem cells, and fetal spinal cord tissue) have already been translated to the clinical arena, whereas others have imminent likelihood of bench-to-bedside application. Although this progress has generated considerable enthusiasm about treating what once was thought to be a totally incurable condition, there are many issues to be considered relative to treatment safety and efficacy. The following review reflects on different experimental applications of intraspinal transplantation with consideration of the underlying pathological, pathophysiological, functional, and neuroplastic responses to spinal trauma that such treatments may target along with related issues of procedural and biological safety. The discussion then moves to an overview of ongoing and completed clinical trials to date. The pros and cons of these endeavors are considered, as well as what has been learned from them. Attention is primarily directed at preclinical animal modeling and the importance of patterning clinical trials, as much as possible, according to laboratory experiences.

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“…Briefly, eight individuals with early-stage, probable AD were administered primary autologous fibroblasts, which had been genetically modified to synthesize and secrete NGF, via stereotaxic injections to the CBF. This approach was shown to survive grafting into the brain and provided stable NGF secretion for up to 18 months in animal studies with improvement of cholinergic function and memory (Emerich et al, 1994;Tuszynski et al, 2002;Tuszynski et al, 2005). At 22 months of follow up, no adverse side effects were reported in the clinical trial.…”

Section: Alzheimer's Disease -Treatment Strategiesmentioning

confidence: 97%

Selectivity of Cell Signaling in the Neuronal Response Based on NGF Mutations and Peptidomimetics in the Treatment of Alzheimers Disease

Neet¹,

Mahapatra²,

Mehta³

2011

Alzheimer's Disease Pathogenesis-Core Concepts, Shifting Paradigms and Therapeutic Targets

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New strategies in neural repair

Cited by 12 publications

References 35 publications

Primary afferent terminal sprouting after a cervical dorsal rootlet section in the macaque monkey

Primary afferent terminal sprouting after a cervical dorsal rootlet section in the macaque monkey

Cellular transplantation strategies for spinal cord injury and translational neurobiology

Selectivity of Cell Signaling in the Neuronal Response Based on NGF Mutations and Peptidomimetics in the Treatment of Alzheimers Disease

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