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Article ; Online: Nano-scaled surfaces and sustainable-antibiotic-release from polymeric coating for application on intra-osseous implants and trans-mucosal abutments.

Kunrath, Marcel F / Rubensam, Gabriel / Rodrigues, Felipe V F / Marinowic, Daniel R / Sesterheim, Patrícia / de Oliveira, Sílvia D / Teixeira, Eduardo R / Hubler, Roberto

Colloids and surfaces. B, Biointerfaces

2023 Volume 228, Page(s) 113417

Abstract: Multifunctional surfaces may display the potential to accelerate and promote the healing process around dental implants. However, the initial cellular biocompatibility, molecular activity, and the release of functionalized molecules from these novel ... ...

Abstract	Multifunctional surfaces may display the potential to accelerate and promote the healing process around dental implants. However, the initial cellular biocompatibility, molecular activity, and the release of functionalized molecules from these novel surfaces require extensive investigation for clinical use. Aiming to develop and compare innovative surfaces for application in dental implants, the present study utilized titanium disks, which were treated and divided into four groups: machined (Macro); acid-etched (Micro); anodized-hydrophilic surface (TNTs); and anodized surface coated with a rifampicin-loaded polymeric layer (poly(lactide-co-glycolide), PLGA) (TNTsRIMP). The samples were characterized regarding their physicochemical properties and the cumulative release of rifampicin (RIMP), investigated at different pH values. Additionally, differentiated osteoblasts from mesenchymal cells were used for cell viability and qRT-PCR analysis. Antibacterial properties of each surface treatment were investigated against Staphylococcus epidermidis. TNTsRIMP demonstrated controlled drug release for up to 7 days in neutral pH environments. Osteogenic cell cultures indicated that all the evaluated surfaces showed biocompatibility. The TNTs group revealed up-regulated values for bone-related gene quantification in 7 days, followed by the TNTsRIMP group. Furthermore, the antibiotic-functionalized surface revealed effectiveness to inhibit S. epidermidis and stimulate promising conditions for osteogenic cell behavior. Characteristics such as nanomorphology and hydrophilicity were determinants for the up-regulated quantification of osteogenic biomarkers related to early bone maturation, encouraging application in intra-osseous implant surfaces; in addition, antibiotic-functionalized surfaces demonstrated significant higher antibacterial properties compared to the other groups. Our findings suggest that polymeric-antibiotic-loaded coating might be applied for the prevention of early infections, favoring its application in multifunctional surfaces for intra- and/or trans-mucosal components of dental implants, while, hydrophilic nanotextured surfaces promoted optimistic properties to stimulate early bone-related cell responses, favoring its application in bone-anchored surfaces.
MeSH term(s)	Anti-Bacterial Agents/pharmacology ; Rifampin/pharmacology ; Dental Implants ; Surface Properties ; Cell Differentiation ; Titanium/pharmacology ; Titanium/chemistry ; Osseointegration
Chemical Substances	Anti-Bacterial Agents ; Rifampin (VJT6J7R4TR) ; Dental Implants ; Titanium (D1JT611TNE)
Language	English
Publishing date	2023-06-19
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1500523-9
ISSN	1873-4367 ; 0927-7765
ISSN (online)	1873-4367
ISSN	0927-7765
DOI	10.1016/j.colsurfb.2023.113417
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A new SYBR Green real-time PCR to detect SARS-CoV-2.

Marinowic, D R / Zanirati, G / Rodrigues, F V F / Grahl, M V C / Alcará, A M / Machado, D C / Da Costa, J C

Scientific reports

2021 Volume 11, Issue 1, Page(s) 2224

Abstract: Phylogenetic analysis has demonstrated that the etiologic agent of the 2020 pandemic outbreak is a betacoronavirus named SARS-CoV-2. For public health interventions, a diagnostic test with high sensitivity and specificity is required. The gold standard ... ...

Abstract	Phylogenetic analysis has demonstrated that the etiologic agent of the 2020 pandemic outbreak is a betacoronavirus named SARS-CoV-2. For public health interventions, a diagnostic test with high sensitivity and specificity is required. The gold standard protocol for diagnosis by the Word Health Organization (WHO) is RT-PCR. To detect low viral loads and perform large-scale screening, a low-cost diagnostic test is necessary. Here, we developed a cost-effective test capable of detecting SARS-CoV-2. We validated an auxiliary protocol for molecular diagnosis with the SYBR Green RT-PCR methodology to successfully screen negative cases of SARS-CoV-2. Our results revealed a set of primers with high specificity and no homology with other viruses from the Coronovideae family or human respiratory tract pathogenic viruses, presenting with complementarity only for rhinoviruses/enteroviruses and Legionella spp. Optimization of the annealing temperature and polymerization time led to a high specificity in the PCR products. We have developed a more affordable and swift methodology for negative SARS-CoV-2 screening. This methodology can be applied on a large scale to soften panic and economic burden through guidance for isolation strategies.
MeSH term(s)	COVID-19/diagnosis ; COVID-19 Nucleic Acid Testing/methods ; DNA, Single-Stranded ; Enterovirus ; Genome, Viral ; Humans ; Organic Chemicals ; Phylogeny ; Polymerase Chain Reaction ; Real-Time Polymerase Chain Reaction/methods ; Rhinovirus ; SARS-CoV-2 ; Sensitivity and Specificity ; Temperature ; Viral Load
Chemical Substances	DNA, Single-Stranded ; Organic Chemicals ; SYBR Green I (163795-75-3)
Language	English
Publishing date	2021-01-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-81245-0
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Article ; Online: Nano-scaled surfaces and sustainable-antibiotic-release from polymeric coating for application on intra-osseous implants and trans-mucosal abutments

Kunrath, Marcel F. / Rubensam, Gabriel / Rodrigues, Felipe V.F. / Marinowic, Daniel R. / Sesterheim, Patrícia / de Oliveira, Sílvia D. / Teixeira, Eduardo R. / Hubler, Roberto

Colloids and Surfaces B: Biointerfaces. 2023 Aug., v. 228 p.113417-

2023

Abstract	Multifunctional surfaces may display the potential to accelerate and promote the healing process around dental implants. However, the initial cellular biocompatibility, molecular activity, and the release of functionalized molecules from these novel surfaces require extensive investigation for clinical use. Aiming to develop and compare innovative surfaces for application in dental implants, the present study utilized titanium disks, which were treated and divided into four groups: machined (Macro); acid-etched (Micro); anodized-hydrophilic surface (TNTs); and anodized surface coated with a rifampicin-loaded polymeric layer (poly(lactide-co-glycolide), PLGA) (TNTsRIMP). The samples were characterized regarding their physicochemical properties and the cumulative release of rifampicin (RIMP), investigated at different pH values. Additionally, differentiated osteoblasts from mesenchymal cells were used for cell viability and qRT-PCR analysis. Antibacterial properties of each surface treatment were investigated against Staphylococcus epidermidis. TNTsRIMP demonstrated controlled drug release for up to 7 days in neutral pH environments. Osteogenic cell cultures indicated that all the evaluated surfaces showed biocompatibility. The TNTs group revealed up-regulated values for bone-related gene quantification in 7 days, followed by the TNTsRIMP group. Furthermore, the antibiotic-functionalized surface revealed effectiveness to inhibit S. epidermidis and stimulate promising conditions for osteogenic cell behavior. Characteristics such as nanomorphology and hydrophilicity were determinants for the up-regulated quantification of osteogenic biomarkers related to early bone maturation, encouraging application in intra-osseous implant surfaces; in addition, antibiotic-functionalized surfaces demonstrated significant higher antibacterial properties compared to the other groups. Our findings suggest that polymeric-antibiotic-loaded coating might be applied for the prevention of early infections, favoring its application in multifunctional surfaces for intra- and/or trans-mucosal components of dental implants, while, hydrophilic nanotextured surfaces promoted optimistic properties to stimulate early bone-related cell responses, favoring its application in bone-anchored surfaces.
Keywords	Staphylococcus epidermidis ; biocompatibility ; biomarkers ; bone formation ; cell viability ; drug delivery systems ; genes ; hydrophilicity ; osteoblasts ; pH ; polymers ; rifampicin ; titanium ; Multifunctional surfaces ; Drug-delivery ; Nanotechnology ; Drug-release ; Osseointegration ; Dental implants
Language	English
Dates of publication	2023-08
Publishing place	Elsevier B.V.
Document type	Article ; Online
ZDB-ID	1500523-9
ISSN	1873-4367 ; 0927-7765
ISSN (online)	1873-4367
ISSN	0927-7765
DOI	10.1016/j.colsurfb.2023.113417
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Article ; Online: Notch signaling in human iPS-derived neuronal progenitor lines from Focal Cortical Dysplasia patients.

Majolo, F / Marinowic, D R / Machado, D C / Da Costa, J C

International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience

2018 Volume 69, Page(s) 112–118

Abstract: Focal Cortical Dysplasia (FCD), a common type of Malformations of cortical development, may result from an early disturbance in the migration and final arrangement of the cortical architecture of immature neurons. FCD type II is now known to be due to a ... ...

Abstract	Focal Cortical Dysplasia (FCD), a common type of Malformations of cortical development, may result from an early disturbance in the migration and final arrangement of the cortical architecture of immature neurons. FCD type II is now known to be due to a post-zygotic somatic mutation that involves the mTOR and AKT pathways. The aim of the present study was to investigate the possible differences in neurogenesis and neurodifferentiation of iPSCs (induced pluripotent stem cells) from fibroblasts of individuals affected by FCD type II (2) and normal individuals (2). iPSCs were generated from skin fibroblasts of FCD individuals and healthy individuals. The reprogramming was done through the fibroblasts exposure to viral vectors containing the OCT4, KLF4, SOX2, and c-MYC genes and the clones were characterized by immunohistochemistry. iPSCs were neurodifferentiated and analyzed at the 14th, 22nd and 35th days. We also analyzed the cerebral cortex tissue, fibroblasts and iPSCs cells from the individuals. Through qRT-PCR, the expression of 4 genes involved in Notch signaling process were quantified. In general, individuals with dysplasia presented increase and decrease in the relative quantification in the most genes analyzed compared to control individuals in all processes and study groups. We suggest that, during embryonic neurogenesis, the neural precursor cells of FCD type II individuals present increase and decrease in gene expression in the Notch signaling pathway causing cortical formation disorders and can be seen as a candidate for the developmental changes observed in the cerebral cortex of individuals with FCD type II. This altered gene expression may be related to brain formation with dysplasia.
MeSH term(s)	Cerebral Cortex/cytology ; Child ; Epilepsy/genetics ; Epilepsy/metabolism ; Excitatory Postsynaptic Potentials/genetics ; Female ; Fibroblasts ; Gene Expression Regulation ; Healthy Volunteers ; Humans ; Immunohistochemistry ; Male ; Malformations of Cortical Development, Group I/genetics ; Malformations of Cortical Development, Group I/metabolism ; Middle Aged ; Neural Stem Cells/metabolism ; Neurogenesis/genetics ; Pluripotent Stem Cells/metabolism ; Receptors, Notch/metabolism ; Signal Transduction/genetics ; Skin/cytology
Chemical Substances	Receptors, Notch
Language	English
Publishing date	2018-07-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	605533-3
ISSN	1873-474X ; 0736-5748
ISSN (online)	1873-474X
ISSN	0736-5748
DOI	10.1016/j.ijdevneu.2018.07.006
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Article ; Online: Undernourishment and recurrent seizures early in life impair Long-Term Potentiation and alter NMDAR and AMPAR expression in rat hippocampus.

Wearick-Silva, L E / Sebben, A D / Costa-Ferro, Z S M / Marinowic, D R / Nunes, M L

International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience

2019 Volume 75, Page(s) 13–18

Abstract: Undernourishment is a global issue, especially in developing countries, affecting newborns and children in a vulnerable period of brain development. Previous studies of undernourishment models suggested a relationship between undernourishment and ... ...

Abstract	Undernourishment is a global issue, especially in developing countries, affecting newborns and children in a vulnerable period of brain development. Previous studies of undernourishment models suggested a relationship between undernourishment and epilepsy. The exposure to both undernourishment and recurrent seizures early in life appears to have detrimental effects on the developing brain. This study aims to investigate the neurobiological consequences of undernourishment and recurrent seizures exposure early in life, investigating Long-Term Potentiation (LTP) induction and gene expression of NMDA receptor subunits in the hippocampus during adulthood (P60). Animals were exposed to maternal deprivation protocol from P2 to P15 to control food intake in rat pups and Flurothyl-induced seizures from P7 to P10. Electrophysiological records of hippocampal slices were recorded and gene expression of NR1A, NR2A, NR2B, NR2C, NR2D and BDNF were investigated. Animals exposed to undernourishment or recurrent seizures failed to promote LTP after stimulation. Furthermore, seizure exposure early in life led to increased expression of hippocampal NR1A, NR2A, NR2B, NR2C and NR2D when compared to controls. Interestingly, when animals were exposed to undernourishment paradigm early in life, this upregulation of NDMA subunits was absent. In conclusion, our study showed impaired LTP after undernourishment and recurrent seizures early in life, together with differential expression of NDMA expression in the hippocampus during adulthood.
MeSH term(s)	Animals ; Brain-Derived Neurotrophic Factor/genetics ; Brain-Derived Neurotrophic Factor/metabolism ; Flurothyl ; Gene Expression ; Hippocampus/metabolism ; Long-Term Potentiation/physiology ; Malnutrition/metabolism ; Malnutrition/physiopathology ; Maternal Deprivation ; Rats ; Receptors, AMPA/genetics ; Receptors, AMPA/metabolism ; Receptors, N-Methyl-D-Aspartate/genetics ; Receptors, N-Methyl-D-Aspartate/metabolism ; Seizures/chemically induced ; Seizures/metabolism ; Seizures/physiopathology
Chemical Substances	Brain-Derived Neurotrophic Factor ; Receptors, AMPA ; Receptors, N-Methyl-D-Aspartate ; Flurothyl (9Z467FG2YK)
Language	English
Publishing date	2019-03-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	605533-3
ISSN	1873-474X ; 0736-5748
ISSN (online)	1873-474X
ISSN	0736-5748
DOI	10.1016/j.ijdevneu.2019.03.005
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Article ; Online: Effect of heat treatment on cytotoxicity and polymerization of universal adhesives.

Klein-Junior, Celso Afonso / Sobieray, Kathleen / Zimmer, Roberto / Portella, Fernando Freitas / Reston, Eduardo Galia / Marinowic, Daniel / Hosaka, Keiichi

Dental materials journal

2020 Volume 39, Issue 6, Page(s) 970–975

Abstract: To assess, in vitro, the influence of heat air treatment on cytotoxicity and degree of conversion (DC) of universal self-etch adhesives (Ambar Universal APS, Scotchbond Universal Adhesive, and Tetric N-Bond Universal) in an NIH/3T3 fibroblast cell ... ...

Abstract	To assess, in vitro, the influence of heat air treatment on cytotoxicity and degree of conversion (DC) of universal self-etch adhesives (Ambar Universal APS, Scotchbond Universal Adhesive, and Tetric N-Bond Universal) in an NIH/3T3 fibroblast cell culture. Samples were divided into three groups: 1) no heat treatment (control), 2) 37°C and 3) 60°C heat treatment before photopolymerization. Cytotoxicity was analyzed by MTT assay and the DC by FTIR. All adhesives heated at 60°C showed reduced cytotoxicity levels when compared with those heated at 37°C. In general, DC of Ambar Universal APS presented the highest DC than Scotchbond Universal Adhesive and Tetric N-Bond Universal, and the hot air treatment do not influence the conversion. Heat treatment at 60°C was able to reduce the cytotoxicity of universal self-etch adhesives, even, the heat treatment does not enhances the DC.
MeSH term(s)	Adhesives ; Dental Bonding ; Dental Cements ; Dentin ; Dentin-Bonding Agents ; Hot Temperature ; Materials Testing ; Polymerization ; Resin Cements
Chemical Substances	Adhesives ; Dental Cements ; Dentin-Bonding Agents ; Resin Cements
Language	English
Publishing date	2020-07-02
Publishing country	Japan
Document type	Journal Article
ZDB-ID	605650-7
ISSN	1881-1361 ; 0287-4547
ISSN (online)	1881-1361
ISSN	0287-4547
DOI	10.4012/dmj.2019-103
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Article: The expression of pluripotency genes and neuronal markers after neurodifferentiation in fibroblasts co-cultured with human umbilical cord blood mononuclear cells

Marinowic, D. R / Domingues, M. F / Machado, D. C / DaCosta, J. C

In vitro cellular & developmental biology. 2015 Jan., v. 51, no. 1

2015

Abstract: ... cultured for 7 d and subsequently co-cultured with mouse fibroblast NIH-3T3 cells for 6 d. The pluripotency ... with umbilical cord blood mononuclear fraction for 6 d promoted the reprogramming of these cells, allowing the later ...

Abstract	Human umbilical cord blood is an attractive source of stem cells; however, it has a heterogeneous cell population with few mesenchymal stem cells. Cell reprogramming induced by different methodologies can confer pluripotency to differentiated adult cells. The objective of this study was to evaluate the reprogramming of fibroblasts and their subsequent neural differentiation after co-culture with umbilical cord blood mononuclear cells. Cells were obtained from four human umbilical cords. The mononuclear cells were cultured for 7 d and subsequently co-cultured with mouse fibroblast NIH-3T3 cells for 6 d. The pluripotency of the cells was evaluated by RT-PCR using primers specific for pluripotency marker genes. The pluripotency was also confirmed by adipogenic and osteogenic differentiation. Neural differentiation of the reprogrammed cells was evaluated by immunofluorescence. All co-cultured cells showed adipogenic and osteogenic differentiation capacity. After co-cultivation, cells expressed the pluripotency gene KLF4. Statistically significant differences in cell area, diameter, optical density, and fractal dimension were observed by confocal microscopy in the neurally differentiated cells. Contact in the form of co-cultivation of fibroblasts with umbilical cord blood mononuclear fraction for 6 d promoted the reprogramming of these cells, allowing the later induction of neural differentiation.
Keywords	absorbance ; adults ; blood ; bone formation ; coculture ; cultured cells ; fibroblasts ; fluorescent antibody technique ; genes ; genetic markers ; humans ; mice ; microscopy ; reverse transcriptase polymerase chain reaction ; stem cells ; umbilical cord
Language	English
Dates of publication	2015-01
Size	p. 26-35.
Publishing place	Springer-Verlag
Document type	Article
ISSN	1071-2690
DOI	10.1007/s11626-014-9804-8
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Article ; Online: A new SYBR Green real-time PCR to detect SARS-CoV-2

D. R. Marinowic / G. Zanirati / F. V. F. Rodrigues / M. V. C. Grahl / A. M. Alcará / D. C. Machado / J. C. Da Costa

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 11

Abstract: Abstract Phylogenetic analysis has demonstrated that the etiologic agent of the 2020 pandemic outbreak is a betacoronavirus named SARS-CoV-2. For public health interventions, a diagnostic test with high sensitivity and specificity is required. The gold ... ...

Abstract	Abstract Phylogenetic analysis has demonstrated that the etiologic agent of the 2020 pandemic outbreak is a betacoronavirus named SARS-CoV-2. For public health interventions, a diagnostic test with high sensitivity and specificity is required. The gold standard protocol for diagnosis by the Word Health Organization (WHO) is RT-PCR. To detect low viral loads and perform large-scale screening, a low-cost diagnostic test is necessary. Here, we developed a cost-effective test capable of detecting SARS-CoV-2. We validated an auxiliary protocol for molecular diagnosis with the SYBR Green RT-PCR methodology to successfully screen negative cases of SARS-CoV-2. Our results revealed a set of primers with high specificity and no homology with other viruses from the Coronovideae family or human respiratory tract pathogenic viruses, presenting with complementarity only for rhinoviruses/enteroviruses and Legionella spp. Optimization of the annealing temperature and polymerization time led to a high specificity in the PCR products. We have developed a more affordable and swift methodology for negative SARS-CoV-2 screening. This methodology can be applied on a large scale to soften panic and economic burden through guidance for isolation strategies.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The expression of pluripotency genes and neuronal markers after neurodifferentiation in fibroblasts co-cultured with human umbilical cord blood mononuclear cells.

Marinowic, D R / Domingues, M F / Machado, D C / DaCosta, J C

In vitro cellular & developmental biology. Animal

2014 Volume 51, Issue 1, Page(s) 26–35

Abstract	Human umbilical cord blood is an attractive source of stem cells; however, it has a heterogeneous cell population with few mesenchymal stem cells. Cell reprogramming induced by different methodologies can confer pluripotency to differentiated adult cells. The objective of this study was to evaluate the reprogramming of fibroblasts and their subsequent neural differentiation after co-culture with umbilical cord blood mononuclear cells. Cells were obtained from four human umbilical cords. The mononuclear cells were cultured for 7 d and subsequently co-cultured with mouse fibroblast NIH-3T3 cells for 6 d. The pluripotency of the cells was evaluated by RT-PCR using primers specific for pluripotency marker genes. The pluripotency was also confirmed by adipogenic and osteogenic differentiation. Neural differentiation of the reprogrammed cells was evaluated by immunofluorescence. All co-cultured cells showed adipogenic and osteogenic differentiation capacity. After co-cultivation, cells expressed the pluripotency gene KLF4. Statistically significant differences in cell area, diameter, optical density, and fractal dimension were observed by confocal microscopy in the neurally differentiated cells. Contact in the form of co-cultivation of fibroblasts with umbilical cord blood mononuclear fraction for 6 d promoted the reprogramming of these cells, allowing the later induction of neural differentiation.
MeSH term(s)	Animals ; Biomarkers/metabolism ; Cell Differentiation/genetics ; Cell Proliferation ; Coculture Techniques/methods ; Fibroblasts/cytology ; Fluorescent Antibody Technique ; Gene Expression Regulation ; Humans ; Imaging, Three-Dimensional ; Interleukin-2/metabolism ; Leukocytes, Mononuclear/cytology ; Leukocytes, Mononuclear/metabolism ; Mesoderm/cytology ; Mice ; NIH 3T3 Cells ; Neurons/cytology ; Neurons/metabolism ; Pluripotent Stem Cells/cytology ; Pluripotent Stem Cells/metabolism ; Umbilical Cord/cytology
Chemical Substances	Biomarkers ; Interleukin-2
Language	English
Publishing date	2014-08-19
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1077810-x
ISSN	1543-706X ; 0883-8364 ; 1071-2690
ISSN (online)	1543-706X
ISSN	0883-8364 ; 1071-2690
DOI	10.1007/s11626-014-9804-8
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Zs.A 851: Show issues

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Article ; Online: The dose-response effect of acute intravenous transplantation of human umbilical cord blood cells on brain damage and spatial memory deficits in neonatal hypoxia-ischemia.

de Paula, S / Greggio, S / Marinowic, D R / Machado, D C / DaCosta, J Costa

Neuroscience

2012 Volume 210, Page(s) 431–441

Abstract: Despite the beneficial effects of cell-based therapies on brain repair shown in most studies, there has not been a consensus regarding the optimal dose of human umbilical cord blood cells (HUCBC) for neonatal hypoxia-ischemia (HI). In this study, we ... ...

Abstract	Despite the beneficial effects of cell-based therapies on brain repair shown in most studies, there has not been a consensus regarding the optimal dose of human umbilical cord blood cells (HUCBC) for neonatal hypoxia-ischemia (HI). In this study, we compared the long-term effects of intravenous administration of HUCBC at three different doses on spatial memory and brain morphological changes after HI in newborn Wistar rats. In addition, we tested whether the transplanted HUCBC migrate to the injured brain after transplantation. Seven-day-old animals underwent right carotid artery occlusion and were exposed to 8% O(2) inhalation for 2 h. After 24 h, randomly selected animals were assigned to four different experimental groups: HI rats administered with vehicle (HI+vehicle), HI rats treated with 1×10(6) (HI+low-dose), 1×10(7) (HI+medium-dose), and 1×10(8) (HI+high-dose) HUCBC into the jugular vein. A control group (sham-operated) was also included in this study. After 8 weeks of transplantation, spatial memory performance was assessed using the Morris water maze (MWM), and subsequently, the animals were euthanized for brain morphological analysis using stereological methods. In addition, we performed immunofluorescence and polymerase chain reaction (PCR) analyses to identify HUCBC in the rat brain 7 days after transplantation. The MWM test showed a significant spatial memory recovery at the highest HUCBC dose compared with HI+vehicle rats (P<0.05). Furthermore, the brain atrophy was also significantly lower in the HI+medium- and high-dose groups compared with the HI+vehicle animals (P<0.01; 0.001, respectively). In addition, HUCBC were demonstrated to be localized in host brains by immunohistochemistry and PCR analyses 7 days after intravenous administration. These results revealed that HUCBC transplantation has the dose-dependent potential to promote robust tissue repair and stable cognitive improvement after HI brain injury.
MeSH term(s)	Animals ; Animals, Newborn ; Brain/pathology ; Cord Blood Stem Cell Transplantation/methods ; Disease Models, Animal ; Fetal Blood/transplantation ; Fluorescent Antibody Technique ; Humans ; Hypoxia-Ischemia, Brain/complications ; Hypoxia-Ischemia, Brain/surgery ; Maze Learning ; Memory ; Memory Disorders/etiology ; Memory Disorders/prevention & control ; Microscopy, Confocal ; Rats ; Rats, Wistar
Language	English
Publishing date	2012-05-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	196739-3
ISSN	1873-7544 ; 0306-4522
ISSN (online)	1873-7544
ISSN	0306-4522
DOI	10.1016/j.neuroscience.2012.03.009
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