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Mol Neurobiol. 2018 Jan;55(1):300-311. doi: 10.1007/s12035-017-0742-9.

Co-Administration of TiO2 Nanowired Mesenchymal Stem Cells with Cerebrolysin Potentiates Neprilysin Level and Reduces Brain Pathology in Alzheimer's Disease.

Author information

1
Department of Surgical Sciences, Anesthesiology & Intensive Care Medicine, Uppsala University Hospital, Uppsala University, SE-75185, Uppsala, Sweden. Sharma@surgsci.uu.se.
2
International Experimental Central Nervous System Injury & Repair (IECNSIR), University Hospital, Uppsala University, Frödingsgatan 12, Bldg. 28, SE-75421, Uppsala, Sweden. Sharma@surgsci.uu.se.
3
Department of Clinical Neurosciences, University of Medicine & Pharmacy, Cluj-Napoca, Romania. Sharma@surgsci.uu.se.
4
Department of Neurosciences, University of Basque Country, Bilbao, Spain. Sharma@surgsci.uu.se.
5
Department of Clinical Neurosciences, University of Medicine & Pharmacy, Cluj-Napoca, Romania.
6
"RoNeuro" Institute for Neurological Research and Diagnostic, 37 Mircea Eliade Street, 400364, Cluj-Napoca, Romania.
7
Department of Neurosciences, University of Basque Country, Bilbao, Spain.
8
Nanoneurosurgery Group, BioCruces Health Research Institute, 48903, Barakaldo, Bizkaia, Spain.
9
Faculty of Health Science, Universidad Autónoma de Chile, Santiago de Chile, Chile.
10
School of Biomedical Engineering, Department of Biomaterials, Indian Institute of technology, Banaras Hindu University, Varanasi, India.
11
Department of Chemistry & Biochemistry, University of Arkansas, Fayetteville, AR, USA.
12
Department of Biomedical Engineering, University of Arkansas, Fayetteville, AR, USA.
13
Department of Pathology, University of Maryland, Baltimore, MD, USA.
14
Department of Surgical Sciences, Anesthesiology & Intensive Care Medicine, Uppsala University Hospital, Uppsala University, SE-75185, Uppsala, Sweden.
15
International Experimental Central Nervous System Injury & Repair (IECNSIR), University Hospital, Uppsala University, Frödingsgatan 12, Bldg. 28, SE-75421, Uppsala, Sweden.

Abstract

Neprilysin (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.

KEYWORDS:

Alzheimer’s disease (AD); Amyloid-beta peptide (aβP); Cerebrolysin (CBL); Mesenchymal stem cells (MSCs); Nanodelivery; Neprilysin (NPL); TiO2 nanowires

PMID:
28844104
DOI:
10.1007/s12035-017-0742-9
[Indexed for MEDLINE]

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