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- W2147406934 abstract "Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by synaptic dysfunction and neuronal loss. Stem cell grafts have been investigated as neurorestorative therapies in neurodegenerative disorders such as AD but their use has been hampered by poor survival of grafted cells. Supply of neurotrophic factors to grafted cells has been proposed as a way to augment survival. We investigated the use of Cerebrolysin (CBL), a peptidergic mixture with neurotrophic-like properties, as an adjunct to stem cell therapy in the APP transgenic (tg) model of AD. CBL has been reported to promote synapse formation, reduce the behavioral deficits in APP tg mice, enhance survival of neuronal stem cells (NSC) and promote endogenous neurogenesis in APP tg mouse models. NSC (derived from fetal mouse cortex) were injected into the hippocampus of non-tg and APP tg mice. Grated cells were tagged with GFP and BrdU to allow quantitative analysis. Simultaneously, mice receive IP either saline or CBL. Groups were assessed at 3, 6 and 9 months after grafting; both groups were treated with CBL until sacrifice. At 3 and 6 months post grafting there was greater survival of NSCs in the vehicle-treated mice non-tg mice compared to vehicle-treated APP tg mice. Compared to vehicle-treated non-tg mice, 6 months post surgery in the APP mice only few of the grafted NSCs (less than 1%) were found. In contrast CBL treatment enhanced the survival of NPCs in both non-tg and APP tg groups above the baseline levels. Most of the surviving NSCs remained as neuroblasts. In the graft area of mice treated with CBL, caspase-3 and TUNEL positive cells were decreased and levels of BDNF were increased. No evidence of tumor growth was detected. Levels of synaptic and dendritic markers were increased in the hippocampus of the grafted non-tg and APP tg mice treated with CBL compared to controls. CBL increases the survival of NSCs even in the hostile APP tg environment. These observations indicate that CBL constitutes an efficient compound to support the survival of grated NSC and may thereby support their therapeutic efficacy." @default.
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- W2147406934 date "2014-07-01" @default.
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- W2147406934 title "P4-204: NEURO-PEPTIDE TREATMENT WITH CEREBROLYSIN IMPROVES THE SURVIVAL OF NEURAL STEM CELL GRAFTS IN THE APP TRANSGENIC MODEL OF ALZHEIMER'S DISEASE" @default.
- W2147406934 doi "https://doi.org/10.1016/j.jalz.2014.05.1722" @default.
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