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- Collin, Tove, et al.
(författare)
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Quantitative analysis of the generation of different striatal neuronal subtypes in the adult brain following excitotoxic injury.
- 2005
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 195:1, s. 71-80
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Tidskriftsartikel (refereegranskat)abstract
- Recent findings in adult rodents have provided evidence for the formation of new striatal neurons from subventricular zone (SVZ) precursors following stroke. Little is known about which factors determine the magnitude of striatal neurogenesis in the damaged brain. Here we studied striatal neurogenesis following an excitotoxic lesion to the adult rat striatum induced by intrastriatal quinolinic acid (QA) infusion. New cells were labeled with the thymidine-analogue 5-bromo-2'-deoxyuridine (BrdU) and their identity was determined immunocytochemically with various phenotypic markers. The unilateral lesion gave rise to increased cell proliferation mainly in the ipsilateral SVZ. At 2 weeks following the insult, there was a pronounced increase of the number of new neurons co-expressing BrdU and a marker of migrating neuroblasts, doublecortin, in the ipsilateral striatum, particularly its non-damaged medial parts. About 80% of the new neurons survived up to 6 weeks, when they expressed the mature neuronal marker NeuN and were preferentially located in the outer parts of the damaged area. Lesion-generated neurons expressed phenotypic markers of striatal medium spiny neurons (DARPP-32) and intemeurons (parvalbumin or neuropeptide Y). The magnitude of neurogenesis correlated to the size of the striatal damage. Our data show for the first time that an excitotoxic lesion to the striatum can trigger the formation of new striatal neurons with phenotypes of both projection neurons and interneurons.
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| 2. |
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| 3. |
- Lindvall, Olle, et al.
(författare)
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Encapsulated cell biodelivery of GDNF: A novel clinical strategy for neuroprotection and neuroregeneration in Parkinson's disease?
- 2008
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 209:1, s. 82-88
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Tidskriftsartikel (refereegranskat)abstract
- The main pathology underlying disease symptoms in Parkinson's disease (PD) is a progressive degeneration of nigrostriatal dopamine (DA) neurons. No effective disease-modifying treatment currently exists. Glial cell line-derived neurotrophic factor (GDNF) has neuroprotective and neuroregenerative effects and it enhances dopaminergic function in animal models of PD. These findings raise the possibility that intrastriatal administration of GDNF might be developed into a new clinical strategy for functional preservation and restoration also in PD patients. Gene therapy is a novel toot to increase local levels of GDNF. Transplantation of encapsulated, GDNF-secreting cells is one strategy for ex vivo cell-based gene delivery which has the advantage to allow for removal of the cells if untoward effects occur. Here we summarize studies with such cells in animals, and discuss the results from previous trials with GDNF in PD patients and their implications for the further development of neuroprotective/neuroregenerative therapies. Finally, we describe the different scientific and regulatory issues that need to be addressed in order to reach the clinic and start the first trial in patients. (c) 2007 Elsevier Inc. All rights reserved.
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