TY  - JOUR
AU  - Vesković, Ana
AU  - Nakarada, Đura
AU  - Pavićević, Aleksandra
AU  - Prokić, Bogomir
AU  - Perović, Milka
AU  - Kanazir, Selma
AU  - Popović-Bijelić, Ana
AU  - Mojović, Miloš
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4221
AB  - BACKGROUND Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by cognitive decline and total brain atrophy. Despite the substantial scientific effort, the pathological mechanisms underlying neurodegeneration in AD are currently unknown. In most studies, amyloid β peptide has been considered the key pathological change in AD. However, numerous Aβ-targeting treatments have failed in clinical trials. This implies the need to shift the re- search focus from Aβ to other pathological features of the disease. OBJECTIVE The aim of this study was to examine the interplay between mitochondrial dysfunction, oxidative stress and blood-brain barrier (BBB) disruption in AD pathology, using a novel approach that involves the application of electron paramagnetic resonance (EPR) spectroscopy. METHOD In vivo and ex vivo EPR spectroscopy using two spin probes (aminoxyl radicals) exhibit- ing different cell-membrane and BBB permeability were employed to assess BBB integrity and brain tissue redox status in the 5xFAD mouse model of AD. In vivo spin probe reduction decay was analyzed using a two-compartment pharmacokinetic model. Furthermore, 15 K EPR spectros- copy was employed to investigate the brain metal content. RESULTS This study has revealed an altered brain redox state, BBB breakdown, as well as ROS-me- diated damage to mitochondrial iron-sulfur clusters, and up-regulation of MnSOD in the 5xFAD model. CONCLUSION The EPR spin probes were shown to be excellent in vivo reporters of the 5xFAD neu- ronal tissue redox state, as well as the BBB integrity, indicating the importance of in vivo EPR spec- troscopy application in preclinical studies of neurodegenerative diseases.
PB  - Bentham Science Publishers Ltd.
T2  - Current Alzheimer Research
T1  - In vivo/Ex Vivo EPR Investigation of the Brain Redox Status and Blood--Brain Barrier Integrity in the 5xFAD Mouse Model of Alzheimer's Disease.
IS  - 1
VL  - 18
DO  - 10.2174/1567205018666210324121156
SP  - 25
EP  - 34
ER  - 

@article{
author = "Vesković, Ana and Nakarada, Đura and Pavićević, Aleksandra and Prokić, Bogomir and Perović, Milka and Kanazir, Selma and Popović-Bijelić, Ana and Mojović, Miloš",
year = "2021",
abstract = "BACKGROUND Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by cognitive decline and total brain atrophy. Despite the substantial scientific effort, the pathological mechanisms underlying neurodegeneration in AD are currently unknown. In most studies, amyloid β peptide has been considered the key pathological change in AD. However, numerous Aβ-targeting treatments have failed in clinical trials. This implies the need to shift the re- search focus from Aβ to other pathological features of the disease. OBJECTIVE The aim of this study was to examine the interplay between mitochondrial dysfunction, oxidative stress and blood-brain barrier (BBB) disruption in AD pathology, using a novel approach that involves the application of electron paramagnetic resonance (EPR) spectroscopy. METHOD In vivo and ex vivo EPR spectroscopy using two spin probes (aminoxyl radicals) exhibit- ing different cell-membrane and BBB permeability were employed to assess BBB integrity and brain tissue redox status in the 5xFAD mouse model of AD. In vivo spin probe reduction decay was analyzed using a two-compartment pharmacokinetic model. Furthermore, 15 K EPR spectros- copy was employed to investigate the brain metal content. RESULTS This study has revealed an altered brain redox state, BBB breakdown, as well as ROS-me- diated damage to mitochondrial iron-sulfur clusters, and up-regulation of MnSOD in the 5xFAD model. CONCLUSION The EPR spin probes were shown to be excellent in vivo reporters of the 5xFAD neu- ronal tissue redox state, as well as the BBB integrity, indicating the importance of in vivo EPR spec- troscopy application in preclinical studies of neurodegenerative diseases.",
publisher = "Bentham Science Publishers Ltd.",
journal = "Current Alzheimer Research",
title = "In vivo/Ex Vivo EPR Investigation of the Brain Redox Status and Blood--Brain Barrier Integrity in the 5xFAD Mouse Model of Alzheimer's Disease.",
number = "1",
volume = "18",
doi = "10.2174/1567205018666210324121156",
pages = "25-34"
}

Vesković, A., Nakarada, Đ., Pavićević, A., Prokić, B., Perović, M., Kanazir, S., Popović-Bijelić, A.,& Mojović, M.. (2021). In vivo/Ex Vivo EPR Investigation of the Brain Redox Status and Blood--Brain Barrier Integrity in the 5xFAD Mouse Model of Alzheimer's Disease.. in Current Alzheimer Research
Bentham Science Publishers Ltd.., 18(1), 25-34.
https://doi.org/10.2174/1567205018666210324121156

Vesković A, Nakarada Đ, Pavićević A, Prokić B, Perović M, Kanazir S, Popović-Bijelić A, Mojović M. In vivo/Ex Vivo EPR Investigation of the Brain Redox Status and Blood--Brain Barrier Integrity in the 5xFAD Mouse Model of Alzheimer's Disease.. in Current Alzheimer Research. 2021;18(1):25-34.
doi:10.2174/1567205018666210324121156 .

Vesković, Ana, Nakarada, Đura, Pavićević, Aleksandra, Prokić, Bogomir, Perović, Milka, Kanazir, Selma, Popović-Bijelić, Ana, Mojović, Miloš, "In vivo/Ex Vivo EPR Investigation of the Brain Redox Status and Blood--Brain Barrier Integrity in the 5xFAD Mouse Model of Alzheimer's Disease." in Current Alzheimer Research, 18, no. 1 (2021):25-34,
https://doi.org/10.2174/1567205018666210324121156 . .

TY  - JOUR
AU  - Živadinović, Milka
AU  - Andrić, Miroslav
AU  - Milošević, Verica
AU  - Manojlović-Stojanoski, Milica
AU  - Prokić, Branislav
AU  - Prokić, Bogomir
AU  - Dimić, Aleksandar
AU  - Ćalasan, Dejan
AU  - Brković, Božidar
PY  - 2016
UR  - http://www.doiserbia.nb.rs/Article.aspx?ID=0042-84501600013Z
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2502
AB  - Background/Aim. The mechanism of impaired bone healing in diabetes mellitus includes different tissue and cellular level activities due to micro- and macrovascular changes. As a chronic metabolic disease with vascular complications, diabetes affects a process of bone regeneration as well. The therapeutic approach in bone regeneration is based on the use of osteoinductive autogenous grafts as well as osteoconductive synthetic material, like a β-tricalcium phosphate. The aim of the study was to determine the quality and quantity of new bone formation after the use of autogenous bone and β-tricalcium phosphate in the model of calvarial critical-sized defect in rabbits with induced diabetes mellitus type I. Methods. The study included eight 4-month-old Chincilla rabbits with alloxan-induced diabetes mellitus type I. In all animals, there were surgically created two calvarial bilateral defects (diameter 12 mm), which were grafted with autogenous bone and β-tricalcium phosphate (n = 4) or served as unfilled controls (n = 4). After 4 weeks of healing, animals were sacrificed and calvarial bone blocks were taken for histologic and histomorphometric analysis. Beside descriptive histologic evaluation, the percentage of new bone formation, connective tissue and residual graft were calculated. All parameters were statistically evaluated by Friedman Test and post hock Wilcoxon Singed Ranks Test with a significance of p < 0.05. Results. Histology revealed active new bone formation peripherally with centrally located connective tissue, newly formed woven bone and well incorporated residual grafts in all treated defects. Control samples showed no bone bridging of defects. There was a significantly more new bone in autogeonous graft (53%) compared with β-tricalcium phosphate (30%), (p < 0.030) and control (7%), (p < 0.000) groups. A significant difference was also recorded between β-tricalcium phosphate and control groups (p < 0.008). Conclusion. In the present study on the rabbit grafting model with induced diabetes mellitus type I, the effective bone regeneration of critical bone defects was obtained using autogenous bone graft.
T2  - Vojnosanitetski pregled
T1  - Histomorphometric evaluation of bone regeneration using autogenous bone and beta-tricalcium phosphate in diabetic rabbits
IS  - 12
VL  - 73
DO  - 10.2298/VSP151125013Z
SP  - 1132
EP  - 1138
ER  - 

@article{
author = "Živadinović, Milka and Andrić, Miroslav and Milošević, Verica and Manojlović-Stojanoski, Milica and Prokić, Branislav and Prokić, Bogomir and Dimić, Aleksandar and Ćalasan, Dejan and Brković, Božidar",
year = "2016",
abstract = "Background/Aim. The mechanism of impaired bone healing in diabetes mellitus includes different tissue and cellular level activities due to micro- and macrovascular changes. As a chronic metabolic disease with vascular complications, diabetes affects a process of bone regeneration as well. The therapeutic approach in bone regeneration is based on the use of osteoinductive autogenous grafts as well as osteoconductive synthetic material, like a β-tricalcium phosphate. The aim of the study was to determine the quality and quantity of new bone formation after the use of autogenous bone and β-tricalcium phosphate in the model of calvarial critical-sized defect in rabbits with induced diabetes mellitus type I. Methods. The study included eight 4-month-old Chincilla rabbits with alloxan-induced diabetes mellitus type I. In all animals, there were surgically created two calvarial bilateral defects (diameter 12 mm), which were grafted with autogenous bone and β-tricalcium phosphate (n = 4) or served as unfilled controls (n = 4). After 4 weeks of healing, animals were sacrificed and calvarial bone blocks were taken for histologic and histomorphometric analysis. Beside descriptive histologic evaluation, the percentage of new bone formation, connective tissue and residual graft were calculated. All parameters were statistically evaluated by Friedman Test and post hock Wilcoxon Singed Ranks Test with a significance of p < 0.05. Results. Histology revealed active new bone formation peripherally with centrally located connective tissue, newly formed woven bone and well incorporated residual grafts in all treated defects. Control samples showed no bone bridging of defects. There was a significantly more new bone in autogeonous graft (53%) compared with β-tricalcium phosphate (30%), (p < 0.030) and control (7%), (p < 0.000) groups. A significant difference was also recorded between β-tricalcium phosphate and control groups (p < 0.008). Conclusion. In the present study on the rabbit grafting model with induced diabetes mellitus type I, the effective bone regeneration of critical bone defects was obtained using autogenous bone graft.",
journal = "Vojnosanitetski pregled",
title = "Histomorphometric evaluation of bone regeneration using autogenous bone and beta-tricalcium phosphate in diabetic rabbits",
number = "12",
volume = "73",
doi = "10.2298/VSP151125013Z",
pages = "1132-1138"
}

Živadinović, M., Andrić, M., Milošević, V., Manojlović-Stojanoski, M., Prokić, B., Prokić, B., Dimić, A., Ćalasan, D.,& Brković, B.. (2016). Histomorphometric evaluation of bone regeneration using autogenous bone and beta-tricalcium phosphate in diabetic rabbits. in Vojnosanitetski pregled, 73(12), 1132-1138.
https://doi.org/10.2298/VSP151125013Z

Živadinović M, Andrić M, Milošević V, Manojlović-Stojanoski M, Prokić B, Prokić B, Dimić A, Ćalasan D, Brković B. Histomorphometric evaluation of bone regeneration using autogenous bone and beta-tricalcium phosphate in diabetic rabbits. in Vojnosanitetski pregled. 2016;73(12):1132-1138.
doi:10.2298/VSP151125013Z .

Živadinović, Milka, Andrić, Miroslav, Milošević, Verica, Manojlović-Stojanoski, Milica, Prokić, Branislav, Prokić, Bogomir, Dimić, Aleksandar, Ćalasan, Dejan, Brković, Božidar, "Histomorphometric evaluation of bone regeneration using autogenous bone and beta-tricalcium phosphate in diabetic rabbits" in Vojnosanitetski pregled, 73, no. 12 (2016):1132-1138,
https://doi.org/10.2298/VSP151125013Z . .