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      HEAVEN: The head anastomosis venture Project outline for the first human head transplantation with spinal linkage (GEMINI)

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          In 1970, the first cephalosomatic linkage was achieved in the monkey. However, the technology did not exist for reconnecting the spinal cord, and this line of research was no longer pursued. In this paper, an outline for the first total cephalic exchange in man is provided and spinal reconnection is described. The use of fusogens, special membrane-fusion substances, is discussed in view of the first human cord linkage. Several human diseases without cure might benefit from the procedure.

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          Rapid, effective, and long-lasting behavioral recovery produced by microsutures, methylene blue, and polyethylene glycol after completely cutting rat sciatic nerves.

          I J Winograd, Stephanie L Kane, Alexsandra Lima … (2012)
          Behavioral function lost in mammals (including humans) after peripheral nerve severance is slowly (weeks to years) and often poorly restored by 1-2-mm/day, nonspecifically directed outgrowths from proximal axonal stumps. To survive, proximal stumps must quickly repair (seal) plasmalemmal damage. We report that, after complete cut- or crush-severance of rat sciatic nerves, morphological continuity, action potential conduction, and behavioral functions can be consistently (>98% of trials), rapidly (minutes to days), dramatically (70-85% recovery), and chronically restored and some Wallerian degeneration prevented. We assess axoplasmic and axolemmal continuity by intra-axonal dye diffusion and action potential conduction across the lesion site and amount of behavioral recovery by Sciatic Functional Index and Foot Fault tests. We apply well-specified sequences of solutions containing FDA-approved chemicals. First, severed axonal ends are opened and resealing is prevented by hypotonic Ca²⁺-free saline containing antioxidants (especially methylene blue) that inhibit plasmalemmal sealing in sciatic nerves in vivo, ex vivo, and in rat B104 hippocampal cells in vitro. Second, a hypotonic solution of polyethylene glycol (PEG) is applied to open closely apposed (by microsutures, if cut) axonal ends to induce their membranes to flow rapidly into each other (PEG-fusion), consistent with data showing that PEG rapidly seals (PEG-seals) transected neurites of B104 cells, independently of any known endogenous sealing mechanism. Third, Ca²⁺-containing isotonic saline is applied to induce sealing of any remaining plasmalemmal holes by Ca²⁺-induced accumulation and fusion of vesicles. These and other data suggest that PEG-sealing is neuroprotective, and our PEG-fusion protocols that repair cut- and crush-severed rat nerves might rapidly translate to clinical procedures. Copyright © 2012 Wiley Periodicals, Inc.
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            Effective Repair of Traumatically Injured Spinal Cord by Nanoscale Block Copolymer Micelles

            Yunzhou Shi, Sungwon Kim, Terry Huff … (2009)
            Spinal cord injury (SCI) results in immediate disruption of neuronal membranes followed by extensive secondary neurodegenerative processes. A key approach for repair of SCI is sealing the damaged membranes early. Here we show that axonal membranes injured by compression can be effectively repaired by using self-assembled monomethoxy poly(ethylene glycol)-poly(D,L-lactic acid) di-block copolymer micelles (60 nm diameter). Injured spinal tissue incubated with micelles showed rapid restoration of compound action potential and reduced calcium influx into axons. Much lower micelle concentration is required for treatment than the positive control, polyethylene glycol. Intravenously injected micelles effectively recovered the locomotor function and reduced the volume and inflammatory response of the lesion in SCI rats. The micelles showed no adverse effects after systemic administration to live rats. Our results suggest that copolymer micelles can interrupt the spread of primary SCI damage with minimal toxicity.
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              Polymer and nano-technology applications for repair and reconstruction of the central nervous system.

              Youngnam Cho, Richard Borgens (2012)
              The hydrophilic polymer PEG and its related derivatives, have served as therapeutic agents to reconstruct the phospholipid bilayers of damaged cell membranes by erasing defects in the plasmalemma. The special attributes of hydrophilic polymers when in contact with cell membranes have been used for several decades since these well-known properties have been exploited in the manufacture of monoclonal antibodies. However, while traditional therapeutic efforts to combat traumatic injuries of the central nervous system (CNS) have not been successful, nanotechnology-based drug delivery has become a new emerging strategy with the additional promise of targeted membrane repair. As such, this potential use of nanotechnology provides new avenues for nanomedicine that uses nanoparticles themselves as the therapeutic agent in addition to their other functionalities. Here we will specifically address new advances in experimental treatment of Spinal Cord and Traumatic Brain injury (SCI and TBI respectively). We focus on the concept of repair of the neurolemma and axolemma in the acute stage of injury, with less emphasis on the worthwhile, and voluminous, issues concerning regenerative medicine/nanomedicine. It is not that the two are mutually exclusive - they are not. However, the survival of the neuron and the tissues of white matter are critical to any further success in what will likely be a multi-component therapy for TBI and SCI. This review includes a brief explanation of the characteristics of traumatic spinal cord injury SCI, the biological basis of the injuries, and the treatment opportunities of current polymer-based therapies. In particular, we update our own progress in such applications for CNS injuries with various suggestions and discussion, primarily nanocarrier-based drug delivery systems. The application of nanoparticles as drug-delivery vehicles to the CNS may likely be advantageous over existing molecular-based therapies. As a "proof-of-concept", we will discuss the recent investigations that have preferentially facilitated repair and functional recovery from breaches in neural membranes via rapid sealing and reassembly of the compromised site with silica or chitosan nanoparticles. Copyright © 2011 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Sergio Canavero
                Journal
                Journal ID (nlm-ta): Surg Neurol Int
                Journal ID (iso-abbrev): Surg Neurol Int
                Journal ID (publisher-id): SNI
                Title: Surgical Neurology International
                Publisher: Medknow Publications & Media Pvt Ltd (India )
                ISSN (Print): 2229-5097
                ISSN (Electronic): 2152-7806
                Publication date Collection: 2013
                Publication date (Electronic): 13 June 2013
                Volume: 4
                Issue: Suppl 1 , SNI: Neurosurgical Developments on the Horizon, a supplement to SNI
                Pages: S335-S342
                Affiliations
                [1]Turin Advanced Neuromodulation Group, Turin, Italy
                Author notes
                [* ]Corresponding author
                Article
                Publisher ID: SNI-4-335
                DOI: 10.4103/2152-7806.113444
                PMC ID: 3821155
                PubMed ID: 24244881
                SO-VID: c18b20c3-769a-44da-893b-94324f25fce8
                Copyright © Copyright: © 2013 Canavero S
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 29 March 2013
                Date received : 10 May 2013
                Categories
                Subject: Surgical Neurology International: Neurosurgical Developments on the Horizon

                ScienceOpen disciplines: Surgery
                Keywords: fusogens,head transplantation,spinal cord reconstruction
                Data availability:
                ScienceOpen disciplines: Surgery
                Keywords: fusogens, head transplantation, spinal cord reconstruction

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