Wyniki wyszukiwania - Biblioteka Nauki

1

Cell-based therapies and functional recovery in experimental stroke rats

100%

Jolkkonen J.

Acta Neurobiologiae Experimentalis

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2009

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tom 69

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nr 1

EN

Stroke is the third leading cause of deaths in Western countries, and more importantly, it is a leading cause of adult disability. Restorative approaches such as cell-based therapies are clinically appealing as it might be possible to help stroke patients even when treatment is initiated days or weeks after the ischemic insult. Noninvasive intravascular administration of cells, which provides a broad distribution of cells to the close proximity of ischemic tissue, has perhaps the most immediate access to clinical applications. For example, intravenous infusion of human umbilical cord blood (HUCB) cells and bone marrow stromal (BMS) cells has been shown to improve sensorimotor functions in rats subjected to focal cerebral ischemia. Interestingly, entry of cells into the central nervous system is not needed for the benefi cial effect indicating that peripheral mechanisms or trophic factors may play a role. Another approach is a stereotaxic transplantation of cells into the brain. Our recent data suggest, that subventricular zone (SVZ)-derived mouse neural stem cells or human embryonic stem cell (hESC)-derived neural precursors, when transplanted close to the infarct, do provide some improvement in sensorimotor function after focal cerebral ischemia in rats, but do not restore more complicated sensorimotor function such as skilled reaching. The major problem seems to be a marginal long-term survival rate of transplanted cells. Thus, more work is needed to defi ne the optimal cell type, route of administration, and timing of administration after cerebral ischemia to support cell survival. This would also ensure safe and effective translation of experimental results into clinical practice.

2

Experimental approaches to enhance functional recovery following cerebral ischemia

100%

Jolkkonen J.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr 1

EN

Stroke is a major cause of adult disability that poses an enormous healthcare burden. Effective pharmacotherapy for stroke remains an unmet need. Development of restorative therapies has been identified as a potential alternative in stroke. Emerging understanding of brain repair and plasticity mechanisms have revealed therapeutic targets including inhibition of axonal sprouting (e.g., Nogo, MAG), altered perilesional GABA and glutamate receptor signaling, endogenous neurogenesis and angiogenesis. The main advantage with restorative therapies is the delayed treatment after acute necrotic cell death, when patients are stable. In addition, restorative therapies can be combined with intensive rehabilitation and medication for poststroke complications to further facilitate recovery process. The problem with patient studies is, however, that many pharmaceutical companies have scaled down their stroke programs, because of failures with neuroprotective compounds. We should convince industry that restorative drugs target completely different mechanisms with extended therapeutic time window offering an attractive approach to help stroke patients.

3

Challenges and possibilities of intravascular cell therapy in stroke

63%

Hicks A. , Jolkkonen J.

Acta Neurobiologiae Experimentalis

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2009

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tom 69

|

nr 1

EN

Stroke is the third leading cause of death in Western countries and more importantly a leading cause of adult disability. The recovery process of stroke patients might be enhanced by intensive rehabilitation, which acts through brain plasticity mechanisms. Restorative approaches such as cell-based therapies are clinically appealing as it might be possible to help patients even when treatment is initiated days or weeks after the ischemic insult. An extensive number of experimental transplantation studies have been conducted with cells of different origins (e.g., embryonic stem, fetal neural stem, human umbilical cord blood) with promising results. Noninvasive intravascular administration of cells, which provides a broad distribution of cells to the close proximity of ischemic tissue, has perhaps the most immediate access to clinical applications. However, surprisingly little is known about whole body biodistribution of intravascularly administered cells and mechanisms leading to improved functional recovery. This review examines the recent literature concerning intravascular cell-based therapies in experimental stroke.

4

Restorative therapies to enhance sensorimotor recovery following cerebral ischemia

63%

Ortega F. J. , Jolkkonen J.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr 1

EN

The development of therapies that aim to facilitate functional recovery has identified potential approaches in stroke research. The main advantage of restorative therapies is their delayed administration after acute necrotic cell death, when the treatment can be combined with intensive rehabilitation and medication for poststroke complications to further enhance therapeutic benefit. Emerging understanding of brain repair and plasticity mechanisms after cerebral insults has revealed novel therapeutic targets including the promotion of axonal sprouting, altered perilesional GABA and glutamate receptor signaling, and enhancement of angiogenesis and endogenous neurogenesis. Interestingly, it seems that intensive rehabilitative training such as constraint-induced movement therapy also acts through these brain repair mechanisms, which may have an additive impact on functional recovery.

5

Human cord blood CD 34 plus cells and behavioral recovery following focal cerebral ischemia in rats

51%

Nystedt J. , Makinen S. , Laine J. , Jolkkonen J.

Acta Neurobiologiae Experimentalis

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2006

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tom 66

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nr 4

EN

The present study investigated effects of human umbilical cord blood derived CD34+ cells on sensorimotor, cognitive, and histological outcome in rats following focal cerebral ischemia. Halothane anesthetized adult male Wistar rats were subjected to transient or permanent occlusion of the middle cerebral artery (MCAO) followed by intravenous administration of CD34+ cells (5 × 105 or 2 × 106) after 24 h recovery. The beam-walking and cylinder tests were used to assess sensorimotor function, and Morris water-maze examined cognitive performance during a 25 day follow-up period. Subsequently, rats were perfused for measurement of infarct volumes and detection of CD34+ cells in the brain by immunohistochemistry (MAB1281). MCAO rats showed minor or no spontaneous recovery in sensorimotor function during the follow-up. The recovery profile was similar in MCAO controls and in MCAO rats that received CD34+ cells, although CD34+ cells seemed to improve the use of impaired forelimb. There was also a trend toward improved water-maze performance by CD34+ cells in transient MCAO rats. Infarct volumes assessed from Nissl-stained sections on postoperative day 25 did not differ between the experimental groups. MAB1281-positive cells were not detected in the brain of MCAO rats that received CD34+ cells. The present study suggests that CD34+ cells might improve functional outcome in MCAO rats after systemic administration, but do not significantly provide neuroprotection.