Implications of Neurological Rehabilitation for Advancing Intracerebral Transplantation

Polgar, Stephen; Borlongan, Cesario V.; Koutouzis, Theodore K.; Todd, Stephanie L; Cahill, David W.; Sanberg, Paul R.

doi:10.1016/s0361-9230(97)00109-3

Cited by 21 publications

(14 citation statements)

References 29 publications

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“…Research designed to improve motor function in stroke patients centers around promoting the use of the affected arm while restricting the opportunity for the intact arm to mediate compensatory strategies (32). It may well be that graft-mediated actions will require similar encouragement, and serious attention will need to be applied to the rehabilitative training of transplanted patients (33).…”

Section: Discussionmentioning

confidence: 99%

Associative plasticity in striatal transplants

Brasted

Watts

Robbins

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

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Striatal lesions disrupt both motor and cognitive performance in rats, many aspects of which can be restored by striatal transplants. Because the normal striatum is involved in the formation and maintenance of motor habits, it has been hypothesized that grafted animals may require explicit retraining to relearn previously established habits that have been disrupted by the lesions. We have used a lateralized-discrimination task to reproduce this ''learning to use the transplant'' effect, combined with a transfer-oftraining paradigm to demonstrate that recovery requires relearning specific lateralized stimulus-response associations and cannot be explained simply by a generalized trainingdependent improvement in motor skill. These results have clear implications for developing appropriate strategies for the rehabilitation of Huntington's disease patients participating in clinical transplantation programs.

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Section: Discussionmentioning

confidence: 99%

Associative plasticity in striatal transplants

Brasted

Watts

Robbins

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

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“…To the contrary, it is known that training or an enriched environment influences neural graft development and morphology in both laboratory animals [30,31] and humans [32,33]. We observed quite poor interactions Table 1 Mean ratio of latencies on the first (D1) and the last day (D10) of the spatial learning test±SEM (standard error of the mean) and mean ratio of trajectory lengths on the first and the last day of the spatial learning test±SEM in individual groups of experimental mice (nerve fibre sprouting, cell migration) between the graft and host cerebellum.…”

Section: Graft Survival and Developmentmentioning

confidence: 99%

The Effect of Cerebellar Transplantation and Enforced Physical Activity on Motor Skills and Spatial Learning in Adult Lurcher Mutant Mice

2008

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Lurcher mutant mice represent a model of olivocerebellar degeneration. They are used to investigate cerebellar functions, consequences of cerebellar degeneration and methods of therapy influencing them. The aim of the work was to assess the effect of foetal cerebellar graft transplantation, repeated enforced physical activity and the combination of both these types of treatment on motor skills, spontaneous motor activity and spatial learning ability in adult B6CBA Lurcher mice. Foetal cerebellar grafts were applied into the cerebellum of Lurchers in the form of solid tissue pieces. Enforced motor activity was realised through rotarod training. Motor functions were examined using bar, ladder and rotarod tests. Spatial learning was tested in the Morris water maze. Spontaneous motor activity in the open field was observed. The presence of the graft was examined histologically. Enforced physical activity led to moderate improvement of some motor skills and to a significant amelioration of spatial learning ability in Lurchers. The transplantation of cerebellar tissue did not influence motor functions significantly but led to an improvement of spatial learning ability. Mutual advancement of the effects of both types of treatment was not observed. Spontaneous motor activity was influenced neither by physical activity nor by the transplantation. Physical activity did not influence the graft survival and development. Because nerve sprouting and cell migration from the graft to the host cerebellum was poor, the functional effects of the graft should be explained with regard to its trophic influence rather than with any involvement of the grafted cells into neural circuitries.

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“…The implications of our developing understanding of graft plasticity for neurological rehabilitation are likely to be profound, but have hitherto been almost totally neglected throughout the cell-therapy field 104 . The standard approach has been to consider biological strategies for repair (whether of neurodegenerative disease, trauma or ischaemia) at the cellular and systems levels, with little further attention given to the patient as a whole organism.…”

Section: Rehabilitation and Therapymentioning

confidence: 99%

The influence of environment and experience on neural grafts

Döbrössy

Dunnett

2001

Nat Rev Neurosci

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An open field with moveable barriers that challenges the animal's learning and memory capabilities in locating a box from a given starting position. 872 | DECEMBER 2001 | VOLUME 2 www.nature.com/reviews/neuro R E V I E W S Cholinergic grafts in cortex and hippocampus. Grafts that are rich in cholinergic neurons derived from the embryonic basal forebrain can reverse various cognitive deficits that are associated with cholinergic depletion in the rat cortex and hippocampus, caused by ageing or explicit lesions 38,39 . In the first model system to be investigated under such conditions, cholinergic fibre outgrowth from basal forebrain tissues, implanted as dissociated cell suspension grafts into the dorsal neocortex, was greater in rats that were housed in an enriched environment than in rats kept in standard cages 40 . The difference was particularly marked at 4 weeks after grafting, but had waned by 10 weeks, indicating that the greatest effect might be on the initial stimulation of neurite growth, rather than asymptotic expansion of the grafts.Further studies analysed the effects of enriched or standard housing on the ability of basal forebrain grafts to alleviate maze-learning deficits in rats with hippocampal cholinergic lesions 41,42 . In the first study, only rats housed for 10 months in an enriched environment after receiving lesions and grafts showed significant attenuation of the profound lesion-induced deficit in relearning a HEBB-WILLIAMS MAZE task; neither the transplant nor enrichment was effective alone 41 . By contrast, a shorter period of enriched housing over 2 months was not sufficient to benefit even the grafted rats. In a second study, rats experienced standard housing alone, standard housing with daily handling and training in a water maze spatial navigation task, or environmental enrichment, before being retested in the Hebb-Williams mazes 42 . Again, neither enrichment nor graft alone was sufficient to sustain recovery over a shorter, 5-month post-surgery period, whereas the specific handling and spatial training did produce selective recovery in the grafted animals. This observation is akin to the finding

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Implications of Neurological Rehabilitation for Advancing Intracerebral Transplantation

Cited by 21 publications

References 29 publications

Associative plasticity in striatal transplants

Associative plasticity in striatal transplants

The Effect of Cerebellar Transplantation and Enforced Physical Activity on Motor Skills and Spatial Learning in Adult Lurcher Mutant Mice

The influence of environment and experience on neural grafts

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