Therapeutic Efficacy of Glial Cell-Derived Neurotrophic Factor Loaded Collagen Scaffolds in ex vivo organotypic brain slice Parkinson's Disease Models.

In this study, we assess the efficacy of collagen scaffolds loaded with GDNF on dopaminergic neuronal survival in organotypic ex vivo slices: axotomy, rotenone, and 6-hydroxydopamine (6-OHDA) models. Coronal (150 µm) mesencephalon brain slices were prepared from postnatal day 9-11 mice. In these slices 424 ± 32 and 158 ± 26 dopamine neurons were found in SN and ventral tegmental area, respectively. Collagen was crosslinked with poly(ethylene glycol), loaded with GDNF and drops of 2 µl collagen scaffold containing 10 ng GDNF were directly placed onto organotypic brain slices. GDNF released from collagen scaffolds significantly protected dopaminergic SN neurons against axotomy and rotenone (50 nM, 14 days) induced cell death and showed a tendency of neuroprotection in 6-OHDA (5 mM, 10 min) lesions. In the axotomy model GDNF (100 ng/ml in medium) markedly enhanced tyrosine hydroxylase (TH) expression, which was verified by Western Blot and qRT-PCR. Our results indicate that this approach has the potential to be used as an injectable hydrogel system to address the need of targeted long-term growth factor delivery for slowing or stopping disease progression in the future. PMID: 31004735 [PubMed - as supplied by publisher]
Source: Brain Research Bulletin - Category: Neurology Authors: Tags: Brain Res Bull Source Type: research

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Source: SafetyLit - Category: International Medicine & Public Health Tags: Age: Elder Adults Source Type: news
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