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| 3. |
- Dunnett, S. B, et al.
(författare)
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Mechanisms and use of neural transplants for brain repair
- 2017
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Ingår i: Functional Neural Transplantation IV Translation to Clinical Application, Part A. - : Elsevier. - 9780128117385 ; 230, s. 1-51
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Bokkapitel (refereegranskat)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 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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| 4. |
- Dunnett, S B, et al.
(författare)
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Intracerebral grafting of neuronal cell suspensions. IV. Behavioural recovery in rats with unilateral implants of nigral cell suspensions in different forebrain sites
- 1983
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Ingår i: Acta Physiologica Scandinavica. ; Suppl. 522, s. 29-38
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Tidskriftsartikel (refereegranskat)abstract
- Single and multiple implants of nigral cell suspensions were grafted to the forebrains of rats with unilateral 6-hydroxydopamine-induced dopamine denervations. Control lesions alone induced a marked behavioural asymmetry, as assessed by amphetamine- and apomorphine-induced rotation, sensorimotor tests and side bias in an unbaited T-maze, and the animals were hyperactive to a low dose of apomorphine. Single suspension placements into different denervated striatal regions were capable of reversing the behavioural asymmetries dependent upon the specific placement for each test. Multiple suspension grafts were capable of reversing all behavioural asymmetries, and additionally abolished the supersensitive hyperactivity to apomorphine. By contrast, single suspension grafts placed into the substantia nigra or lateral hypothalamus had no detectable effect on any functional measure. The results indicate that nigral suspension grafts can be at least as effective as solid grafts in reversing the functional deficits induced by dopamine denervation, provided that placements are selected within appropriate dopamine terminal regions of the forebrain (e.g. caudate-putamen or nucleus accumbens).
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| 5. |
- Dunnett, S B, et al.
(författare)
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Intracerebral grafting of neuronal cell suspensions. V. Behavioural recovery in rats with bilateral 6-OHDA lesions following implantation of nigral cell suspensions.
- 1983
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Ingår i: Acta Physiologica Scandinavica. ; Suppl. 522, s. 39-48
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Tidskriftsartikel (refereegranskat)abstract
- Bilateral 6-hydroxydopamine-induced lesions of the ascending forebrain dopamine neurones induce a behavioural syndrome in rats which includes profound aphagia, adipsia, akinesia and bilateral sensorimotor neglect. Such animals will die unless maintained by intragastric feeding. Three experiments are reported in which we have attempted to ameliorate this syndrome with single or multiple placements of nigral cell suspensions into the forebrains of rats with bilateral dopamine depletions. Although the grafts were efficient in reversing the sensorimotor and akinetic impairments, and produced a significant increase in eating, the grafted rats remained hypophagic and adipsic. The results indicate that although many components of the bilateral dopamine denervation syndrome can be reversed by intrastriatal nigral suspension grafts, the severe eating and drinking deficits remain unameliorated.
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| 6. |
- Dunnett, Stephen B, et al.
(författare)
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Introduction (Part I)
- 2012
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Ingår i: Functional Neural Transplantation III : Primary and stem cell therapies for brain repair. Part 1 - Primary and stem cell therapies for brain repair. Part 1. - 0079-6123. - 9780444595751 ; 200, s. 3-5
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Bokkapitel (refereegranskat)
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| 7. |
- Dunnett, Stephen B, et al.
(författare)
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Introduction (Part II)
- 2012
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Ingår i: Functional Neural Transplantation III : Primary and Stem Cell Therapies for Brain Repair, Part II - Primary and Stem Cell Therapies for Brain Repair, Part II. - 0079-6123. - 9780444595447 ; 201, s. 3-5
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Bokkapitel (refereegranskat)
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| 8. |
- Lindgren, H. S., et al.
(författare)
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The effect of additional noradrenergic and serotonergic depletion on a lateralised choice reaction time task in rats with nigral 6-OHDA lesions
- 2014
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886 .- 1090-2430. ; 253, s. 52-62
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson's disease (PD) patients often suffer from visuospatial deficits, which have been considered a disruption of the representation of external space. The lateralised choice reaction time (CRT) task is an operant task for rodents in which similar deficits can be assessed. It has been demonstrated that specific parameters in this task is disrupted after unilateral injections of 6-hydroxydopamine (6-OHDA), which have been associated with the dopamine (DA) depletion that inevitably follows this type of lesion. However, studies have demonstrated that this type of lesion also affects the serotonergic (5HT) and noradrenergic (NA) systems. However, the impact of these systems on parameters in the CRT task had not yet been investigated.To this end, rats were pretrained on the CRT task before receiving selective lesions of the DAergic system, either alone or in combination with depletion of the NA or 5HT system. All rats with a 6-OHDA lesion displayed a gradual decline in the selection, initiation and execution of lateralised movements compared to sham-lesion controls on the side contralateral to the lesion. They also displayed a reduced number of useable trials as well as an increased number of procedural errors. Interestingly, the group with an additional noradrenergic lesion was significantly slower in reacting to lateralised stimuli throughout the testing period compared to the other two groups with a 6-OHDA lesion. There was however no difference between the three different lesion groups in the other parameters assessed in the task.These data confirm previous findings demonstrating that the majority of the parameters assessed in the lateralised CRT task are strongly dependent on DA. However, this study has also shown that the NAergic system may play an important role in contributing to the attentive performance influencing the capacity to react to the presented lateralised stimuli. © 2013 Elsevier Inc.
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| 10. |
- Björklund, Anders, et al.
(författare)
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Intracerebral grafting of neuronal cell suspensions. I. Introduction and general methods of preparation.
- 1983
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Ingår i: Acta Physiologica Scandinavica. ; Suppl. 522, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- The steps involved in the grafting of mesencephalic and septal embryonic tissue in the form of dissociated cell suspensions are described in detail. This includes dissection of the donor embryos, incubation in trypsin, mechanical dissociation, and stereotaxic injection into the brains of adult recipient rats. Some of the technical problems and limitations are discussed.
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