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Co-administration of TiO2 nanowired mesenchymal stem cells with cerebrolysin potentiates neprilysin level and reduces brain pathology in alzheimer’s disease

dc.contributor.authorSharma H.S.
dc.contributor.authorMuresanu D.F.
dc.contributor.authorLafuente J.V.
dc.contributor.authorPatnaik R.
dc.contributor.authorTian Z.R.
dc.contributor.authorOzkizilcik A.
dc.contributor.authorCastellani R.J.
dc.contributor.authorMössler H.
dc.contributor.authorSharma A.
dc.date.accessioned2020-09-02T22:28:14Z
dc.date.available2020-09-02T22:28:14Z
dc.date.issued2018
dc.identifier10.1007/s12035-017-0742-9
dc.identifier.citation55, 1, 300-311
dc.identifier.issn08937648
dc.identifier.urihttps://hdl.handle.net/20.500.12728/6249
dc.descriptionNeprilysin (NPL), the rate-limiting enzyme for amyloid beta peptide (AβP), appears to play a crucial role in the pathogenesis of Alzheimer’s disease (AD). Since mesenchymal stem cells (MSCs) and/or cerebrolysin (CBL, a combination of neurotrophic factors and active peptide fragments) have neuroprotective effects in various CNS disorders, we examined nanowired delivery of MSCs and CBL on NPL content and brain pathology in AD using a rat model. AD-like symptoms were produced by intraventricular (i.c.v.) administration of AβP (1-40) in the left lateral ventricle (250 ng/10 μl, once daily) for 4 weeks. After 30 days, the rats were examined for NPL and AβP concentrations in the brain and related pathology. Co-administration of TiO2-nanowired MSCs (106 cells) with 2.5 ml/kg CBL (i.v.) once daily for 1 week after 2 weeks of AβP infusion significantly increased the NPL in the hippocampus (400 pg/g) from the untreated control group (120 pg/g; control 420 ± 8 pg/g brain) along with a significant decrease in the AβP deposition (45 pg/g from untreated control 75 pg/g; saline control 40 ± 4 pg/g). Interestingly, these changes were much less evident when the MSCs or CBL treatment was given alone. Neuronal damages, gliosis, and myelin vesiculation were also markedly reduced by the combined treatment of TiO2, MSCs, and CBL in AD. These observations are the first to show that co-administration of TiO2-nanowired CBL and MSCs has superior neuroprotective effects in AD probably due to increasing the brain NPL level effectively, not reported earlier. © Springer Science+Business Media New York 2016.
dc.language.isoen
dc.publisherHumana Press Inc.
dc.subjectAlzheimer’s disease (AD)
dc.subjectAmyloid-beta peptide (aβP)
dc.subjectCerebrolysin (CBL)
dc.subjectMesenchymal stem cells (MSCs)
dc.subjectNanodelivery
dc.subjectNeprilysin (NPL)
dc.subjectTiO2 nanowires
dc.subjectamyloid beta protein[1-40]
dc.subjectcerebrolysin
dc.subjectglial fibrillary acidic protein
dc.subjectmembrane metalloendopeptidase
dc.subjectmyelin
dc.subjectnanowire
dc.subjecttitanium dioxide
dc.subjectamino acid
dc.subjectcerebrolysin
dc.subjectmembrane metalloendopeptidase
dc.subjectnanowire
dc.subjecttitanium
dc.subjecttitanium dioxide
dc.subjectAlzheimer disease
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectArticle
dc.subjectblood brain barrier
dc.subjectbrain edema
dc.subjectcontrolled study
dc.subjectgliosis
dc.subjecthippocampus
dc.subjectmale
dc.subjectmesenchymal stem cell transplantation
dc.subjectnerve cell lesion
dc.subjectneuroprotection
dc.subjectnonhuman
dc.subjectrat
dc.subjectAlzheimer disease
dc.subjectanimal
dc.subjectbiosynthesis
dc.subjectbrain
dc.subjectdrug effect
dc.subjectmesenchymal stem cell transplantation
dc.subjectmetabolism
dc.subjectpathology
dc.subjectprocedures
dc.subjectSprague Dawley rat
dc.subjectAlzheimer Disease
dc.subjectAmino Acids
dc.subjectAnimals
dc.subjectBrain
dc.subjectMale
dc.subjectMesenchymal Stem Cell Transplantation
dc.subjectNanowires
dc.subjectNeprilysin
dc.subjectRats
dc.subjectRats, Sprague-Dawley
dc.subjectTitanium
dc.titleCo-administration of TiO2 nanowired mesenchymal stem cells with cerebrolysin potentiates neprilysin level and reduces brain pathology in alzheimer’s disease
dc.typeArticle


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