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Timed release of cerebrolysin using drug-loaded titanate nanospheres reduces brain pathology and improves behavioral functions in Parkinson’s disease

dc.contributor.authorOzkizilcik A.
dc.contributor.authorSharma A.
dc.contributor.authorMuresanu D.F.
dc.contributor.authorLafuente J.V.
dc.contributor.authorRyan Tian Z.
dc.contributor.authorPatnaik R.
dc.contributor.authorMössler H.
dc.contributor.authorSharma H.S.
dc.date.accessioned2020-09-02T22:25:13Z
dc.date.available2020-09-02T22:25:13Z
dc.date.issued2018
dc.identifier10.1007/s12035-017-0747-4
dc.identifier.citation55, 1, 359-369
dc.identifier.issn08937648
dc.identifier.urihttps://hdl.handle.net/20.500.12728/5703
dc.descriptionPrevious studies from our laboratory show that intraperitoneal injections of 1-metyl-4-phenyl-1,2,3,6- tetrahydropyridin (MPTP, 20 mg/kg) daily within 2-h intervals for 5 days in mice induce Parkinson’s disease (PD)-like symptoms on the 8th day. A significant decrease in dopamine (DA) and its metabolites 3,4- dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) along with a marked decrease in the number of tyrosine hydroxylase (TH)-positive cells in the substantia nigra pars compacta (SNpc) and striatum (STr) confirms the validity of this model for studying PD. Since cerebrolysin (CBL) is a well-balanced composition of several neurotrophic factors and active peptide fragments, in the present investigation we examined the timed release of CBL using titanate nanospheres (TiNS) in treating PD in our mouse model. Our observations show that TiNS-CBL (in a dose of 3 ml/kg, i.v.) given after 2 days of MPTP administration for 5 days resulted in a marked increase in TH-positive cells in the SNpc and STr as compared to normal CBL. Also, TiNS-CBL resulted in significantly higher levels of DA, DOPAC, and HVA in SNpc and STr on the 8th day as compared to normal CBL therapy. TiNS-CBL also thwarted increased a-synuclein levels in the brain and in the cerebrospinal fluid (CSF) as well as neuronal nitric oxide synthase (nNOS) in the in PD brain as compared to untreated group. Behavioral function was also significantly improved in MPTP-treated animals that received TiNS-CBL. These observations are the first to demonstrate that timed release of TiNS-CBL has far more superior neuroprotective effects in PD than normal CBL. © Springer Science+Business Media, LLC 2017.
dc.language.isoen
dc.publisherHumana Press Inc.
dc.subject1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP)
dc.subjectAlpha-synuclein
dc.subjectCerebrolysin
dc.subjectCerebrospinal fluid (CSF)
dc.subjectNeuronal nitoic oxide synthase (nNOS)
dc.subjectNeuroprotection
dc.subjectParkinson’s disease (PD)
dc.subjectTitanate nanospheres (TiNS)
dc.subject1,2,3,6 tetrahydro 1 methyl 4 phenylpyridine
dc.subject3,4 dihydroxyphenylacetic acid
dc.subjectalpha synuclein
dc.subjectcerebrolysin
dc.subjectdopamine
dc.subjecthomovanillic acid
dc.subjectnanosphere
dc.subjectneuronal nitric oxide synthase
dc.subjecttitanate nanosphere
dc.subjecttyrosine 3 monooxygenase
dc.subjectunclassified drug
dc.subjectamino acid
dc.subjectcerebrolysin
dc.subjectdrug carrier
dc.subjectnanosphere
dc.subjecttitanium
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectArticle
dc.subjectblood brain barrier
dc.subjectcerebrospinal fluid
dc.subjectcontrolled study
dc.subjectcorpus striatum
dc.subjectdrug delivery system
dc.subjectdrug formulation
dc.subjecthigh performance liquid chromatography
dc.subjectimmunohistochemistry
dc.subjectin vitro study
dc.subjectin vivo study
dc.subjectmale
dc.subjectmouse
dc.subjectneuroprotection
dc.subjectnonhuman
dc.subjectParkinson disease
dc.subjectprotein expression
dc.subjectscanning electron microscopy
dc.subjectsubstantia nigra pars compacta
dc.subjecttimed drug release
dc.subjectanimal
dc.subjectbrain
dc.subjectC57BL mouse
dc.subjectdrug effect
dc.subjectdrug release
dc.subjectmetabolism
dc.subjectmotor activity
dc.subjectparkinsonism
dc.subjectpathology
dc.subjectphysiology
dc.subjectAmino Acids
dc.subjectAnimals
dc.subjectBrain
dc.subjectDrug Carriers
dc.subjectDrug Liberation
dc.subjectMale
dc.subjectMice
dc.subjectMice, Inbred C57BL
dc.subjectMotor Activity
dc.subjectNanospheres
dc.subjectParkinsonian Disorders
dc.subjectTitanium
dc.titleTimed release of cerebrolysin using drug-loaded titanate nanospheres reduces brain pathology and improves behavioral functions in Parkinson’s disease
dc.typeArticle


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