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Mechanisms and use of neural transplants for brain repair

Dunnett, S. B and Björklund, A. LU (2017) In Progress in Brain Research 230. p.1-51
Abstract

Under appropriate conditions, neural tissues transplanted into the adult mammalian brain can survive, integrate, and function so as to influence the behavior of the host, opening the prospect of repairing neuronal damage, and alleviating symptoms associated with neuronal injury or neurodegenerative disease. Alternative mechanisms of action have been postulated: nonspecific effects of surgery; neurotrophic and neuroprotective influences on disease progression and host plasticity; diffuse or locally regulated pharmacological delivery of deficient neurochemicals, neurotransmitters, or neurohormones; restitution of the neuronal and glial environment necessary for proper host neuronal support and processing; promoting local and long-distance... (More)

Under appropriate conditions, neural tissues transplanted into the adult mammalian brain can survive, integrate, and function so as to influence the behavior of the host, opening the prospect of repairing neuronal damage, and alleviating symptoms associated with neuronal injury or neurodegenerative disease. Alternative mechanisms of action have been postulated: nonspecific effects of surgery; neurotrophic and neuroprotective influences on disease progression and host plasticity; diffuse or locally regulated pharmacological delivery of deficient neurochemicals, neurotransmitters, or neurohormones; restitution of the neuronal and glial environment necessary for proper host neuronal support and processing; promoting local and long-distance host and graft axon growth; formation of reciprocal connections and reconstruction of local circuits within the host brain; and up to full integration and reconstruction of fully functional host neuronal networks. Analysis of neural transplants in a broad range of anatomical systems and disease models, on simple and complex classes of behavioral function and information processing, have indicated that all of these alternative mechanisms are likely to contribute in different circumstances. Thus, there is not a single or typical mode of graft function; rather grafts can and do function in multiple ways, specific to each particular context. Consequently, to develop an effective cell-based therapy, multiple dimensions must be considered: the target disease pathogenesis; the neurodegenerative basis of each type of physiological dysfunction or behavioral symptom; the nature of the repair required to alleviate or remediate the functional impairments of particular clinical relevance; and identification of a suitable cell source or delivery system, along with the site and method of implantation, that can achieve the sought for repair and recovery.

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Please use this url to cite or link to this publication:
author
organization
publishing date
type
Chapter in Book/Report/Conference proceeding
publication status
published
subject
keywords
Brain repair, Bridge grafts, Circuit repair, Functional recovery, Hippocampal grafts, Mechanisms, Neural transplantation, Neuroplasticity, Nigral grafts, Reinnervation, Spinal cord grafts, Striatal grafts, Trophic mechanisms
in
Progress in Brain Research
editor
Dunnett, S.B.; Björklund, A.; and
volume
230
pages
1 - 51
publisher
Elsevier
external identifiers
  • scopus:85017443831
  • wos:000414257100002
ISBN
978-0-12-811738-5
DOI
10.1016/bs.pbr.2016.11.002
language
English
LU publication?
yes
id
5e6da0d7-c5b7-4d21-ab39-13c85ed515a0
date added to LUP
2017-05-08 15:55:50
date last changed
2018-01-16 13:26:04
@inbook{5e6da0d7-c5b7-4d21-ab39-13c85ed515a0,
  abstract     = {<p>Under appropriate conditions, neural tissues transplanted into the adult mammalian brain can survive, integrate, and function so as to influence the behavior of the host, opening the prospect of repairing neuronal damage, and alleviating symptoms associated with neuronal injury or neurodegenerative disease. Alternative mechanisms of action have been postulated: nonspecific effects of surgery; neurotrophic and neuroprotective influences on disease progression and host plasticity; diffuse or locally regulated pharmacological delivery of deficient neurochemicals, neurotransmitters, or neurohormones; restitution of the neuronal and glial environment necessary for proper host neuronal support and processing; promoting local and long-distance host and graft axon growth; formation of reciprocal connections and reconstruction of local circuits within the host brain; and up to full integration and reconstruction of fully functional host neuronal networks. Analysis of neural transplants in a broad range of anatomical systems and disease models, on simple and complex classes of behavioral function and information processing, have indicated that all of these alternative mechanisms are likely to contribute in different circumstances. Thus, there is not a single or typical mode of graft function; rather grafts can and do function in multiple ways, specific to each particular context. Consequently, to develop an effective cell-based therapy, multiple dimensions must be considered: the target disease pathogenesis; the neurodegenerative basis of each type of physiological dysfunction or behavioral symptom; the nature of the repair required to alleviate or remediate the functional impairments of particular clinical relevance; and identification of a suitable cell source or delivery system, along with the site and method of implantation, that can achieve the sought for repair and recovery.</p>},
  author       = {Dunnett, S. B and Björklund, A.},
  editor       = {Dunnett, S.B. and Björklund, A.},
  isbn         = {978-0-12-811738-5},
  keyword      = {Brain repair,Bridge grafts,Circuit repair,Functional recovery,Hippocampal grafts,Mechanisms,Neural transplantation,Neuroplasticity,Nigral grafts,Reinnervation,Spinal cord grafts,Striatal grafts,Trophic mechanisms},
  language     = {eng},
  pages        = {1--51},
  publisher    = {Elsevier},
  series       = {Progress in Brain Research},
  title        = {Mechanisms and use of neural transplants for brain repair},
  url          = {http://dx.doi.org/10.1016/bs.pbr.2016.11.002},
  volume       = {230},
  year         = {2017},
}