TY  - CONF
AU  - Savic, Danijela
AU  - Opačić, Miloš
AU  - Ristic, Aleksandar J
AU  - Sokic, Dragoslav
AU  - Bascarevic, Vladimir
AU  - Raičević, Savo
AU  - Savić, Slobodan
AU  - Živin, Marko
AU  - Šelih, Vid Simon
AU  - Spasic, Snezana
AU  - Spasojević, Ivan
PY  - 2018
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/2961
AB  - The accumulating evidence on the relation between the disturbed metal homeostasis and epilepsy urges the need for data regarding the total metal concentrations, as well as metal distribution in the brain itself, in order to indicate where to direct the potential therapy, to metal supplementation or chelation. This paper summarizes our results on the measurements of some important essential metals in hippocampi of patients with mesial temporal lobe epilepsy (mTLE) who underwent amigdalohippocampectomy. The key findings point out that levels of copper and manganese are deficient in hippocampi of mTLE patients, and that their concentrations correlated positively with neuronal loss in affected regions of sclerotic hippocampus. In addition, the Cu concentration was decreased in the areas of total neuronal loss. Iron and zinc total hippocampal levels were neither accumulated nor deficient compared to control. Our results contribute to deeper insight of metals biology in the epilepsy and may represent the initial point of new and non-invasive therapy of drug resistant epilepsy.
PB  - Biohemijsko društvo Srbije
C3  - Serbian Biochemical Society Eighth Conference with international participation, “Coordination in Biochemistry and Life”, University of Novi Sad – Rectorate Hall, 16.11.2018. Novi Sad, Serbia
T1  - Distribution and role of metals in sclerotic hippocampi of patients with mesial temporal lobe epilepsy
EP  - 112
SP  - 105
UR  - https://hdl.handle.net/21.15107/rcub_rimsi_2961
ER  - 

@conference{
author = "Savic, Danijela and Opačić, Miloš and Ristic, Aleksandar J and Sokic, Dragoslav and Bascarevic, Vladimir and Raičević, Savo and Savić, Slobodan and Živin, Marko and Šelih, Vid Simon and Spasic, Snezana and Spasojević, Ivan",
year = "2018",
abstract = "The accumulating evidence on the relation between the disturbed metal homeostasis and epilepsy urges the need for data regarding the total metal concentrations, as well as metal distribution in the brain itself, in order to indicate where to direct the potential therapy, to metal supplementation or chelation. This paper summarizes our results on the measurements of some important essential metals in hippocampi of patients with mesial temporal lobe epilepsy (mTLE) who underwent amigdalohippocampectomy. The key findings point out that levels of copper and manganese are deficient in hippocampi of mTLE patients, and that their concentrations correlated positively with neuronal loss in affected regions of sclerotic hippocampus. In addition, the Cu concentration was decreased in the areas of total neuronal loss. Iron and zinc total hippocampal levels were neither accumulated nor deficient compared to control. Our results contribute to deeper insight of metals biology in the epilepsy and may represent the initial point of new and non-invasive therapy of drug resistant epilepsy.",
publisher = "Biohemijsko društvo Srbije",
journal = "Serbian Biochemical Society Eighth Conference with international participation, “Coordination in Biochemistry and Life”, University of Novi Sad – Rectorate Hall, 16.11.2018. Novi Sad, Serbia",
title = "Distribution and role of metals in sclerotic hippocampi of patients with mesial temporal lobe epilepsy",
pages = "112-105",
url = "https://hdl.handle.net/21.15107/rcub_rimsi_2961"
}

Savic, D., Opačić, M., Ristic, A. J., Sokic, D., Bascarevic, V., Raičević, S., Savić, S., Živin, M., Šelih, V. S., Spasic, S.,& Spasojević, I.. (2018). Distribution and role of metals in sclerotic hippocampi of patients with mesial temporal lobe epilepsy. in Serbian Biochemical Society Eighth Conference with international participation, “Coordination in Biochemistry and Life”, University of Novi Sad – Rectorate Hall, 16.11.2018. Novi Sad, Serbia
Biohemijsko društvo Srbije., 105-112.
https://hdl.handle.net/21.15107/rcub_rimsi_2961

Savic D, Opačić M, Ristic AJ, Sokic D, Bascarevic V, Raičević S, Savić S, Živin M, Šelih VS, Spasic S, Spasojević I. Distribution and role of metals in sclerotic hippocampi of patients with mesial temporal lobe epilepsy. in Serbian Biochemical Society Eighth Conference with international participation, “Coordination in Biochemistry and Life”, University of Novi Sad – Rectorate Hall, 16.11.2018. Novi Sad, Serbia. 2018;:105-112.
https://hdl.handle.net/21.15107/rcub_rimsi_2961 .

Savic, Danijela, Opačić, Miloš, Ristic, Aleksandar J, Sokic, Dragoslav, Bascarevic, Vladimir, Raičević, Savo, Savić, Slobodan, Živin, Marko, Šelih, Vid Simon, Spasic, Snezana, Spasojević, Ivan, "Distribution and role of metals in sclerotic hippocampi of patients with mesial temporal lobe epilepsy" in Serbian Biochemical Society Eighth Conference with international participation, “Coordination in Biochemistry and Life”, University of Novi Sad – Rectorate Hall, 16.11.2018. Novi Sad, Serbia (2018):105-112,
https://hdl.handle.net/21.15107/rcub_rimsi_2961 .

TY  - JOUR
AU  - Opačić, Miloš
AU  - Stević, Zorica D
AU  - Baščarević, Vladimir
AU  - Zivić, Miroslav
AU  - Spasić, Mihajlo
AU  - Spasojević, Ivan
PY  - 2018
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/1115
AB  - The monitoring of progression in amyotrophic lateral sclerosis (ALS) relies on clinical outcome measures that take months to interpret, such as revised ALS functional rating scale (ALSFRS-R) score, with no approved biomarkers. A number of clinical studies have documented the involvement of oxidative stress in ALS pathology. Pertinent to this, we propose to evaluate oxidation-reduction potential (ORP) of cerebrospinal fluid (CSF) as a potential indicator of ALS progression. The case-control study included 24 patients with neurological non-neurodegenerative disorders (controls) and 82 ALS patients with different degrees of disease (ALSFRS-R score: 21-47). ORP was significantly higher in ALS patients than controls. It was not dependent on age or gender. A strong negative correlation was found between ORP and ALSFRS-R score for all patients and patients with spinal onset. In other words, ORP increased with ALS progression. No correlation was found for the subset of patients with bulbar onset, most likely because of the physical distance between neurodegenerative loci and the site of CSF collection. These results lead to the hypothesis that ORP of CSF has a potential as monitoring biomarker in ALS, particularly in the cohort of patients with spinal onset. Antioxid. Redox Signal. 00, 000-000.
PB  - Mary Ann Liebert, Inc, New Rochelle
T2  - Antioxidants & Redox Signaling
T1  - Can Oxidation-Reduction Potential of Cerebrospinal Fluid Be a Monitoring Biomarker in Amyotrophic Lateral Sclerosis?
EP  - 1575
IS  - 17
SP  - 1570
VL  - 28
DO  - 10.1089/ars.2017.7433
ER  - 

@article{
author = "Opačić, Miloš and Stević, Zorica D and Baščarević, Vladimir and Zivić, Miroslav and Spasić, Mihajlo and Spasojević, Ivan",
year = "2018",
abstract = "The monitoring of progression in amyotrophic lateral sclerosis (ALS) relies on clinical outcome measures that take months to interpret, such as revised ALS functional rating scale (ALSFRS-R) score, with no approved biomarkers. A number of clinical studies have documented the involvement of oxidative stress in ALS pathology. Pertinent to this, we propose to evaluate oxidation-reduction potential (ORP) of cerebrospinal fluid (CSF) as a potential indicator of ALS progression. The case-control study included 24 patients with neurological non-neurodegenerative disorders (controls) and 82 ALS patients with different degrees of disease (ALSFRS-R score: 21-47). ORP was significantly higher in ALS patients than controls. It was not dependent on age or gender. A strong negative correlation was found between ORP and ALSFRS-R score for all patients and patients with spinal onset. In other words, ORP increased with ALS progression. No correlation was found for the subset of patients with bulbar onset, most likely because of the physical distance between neurodegenerative loci and the site of CSF collection. These results lead to the hypothesis that ORP of CSF has a potential as monitoring biomarker in ALS, particularly in the cohort of patients with spinal onset. Antioxid. Redox Signal. 00, 000-000.",
publisher = "Mary Ann Liebert, Inc, New Rochelle",
journal = "Antioxidants & Redox Signaling",
title = "Can Oxidation-Reduction Potential of Cerebrospinal Fluid Be a Monitoring Biomarker in Amyotrophic Lateral Sclerosis?",
pages = "1575-1570",
number = "17",
volume = "28",
doi = "10.1089/ars.2017.7433"
}

Opačić, M., Stević, Z. D., Baščarević, V., Zivić, M., Spasić, M.,& Spasojević, I.. (2018). Can Oxidation-Reduction Potential of Cerebrospinal Fluid Be a Monitoring Biomarker in Amyotrophic Lateral Sclerosis?. in Antioxidants & Redox Signaling
Mary Ann Liebert, Inc, New Rochelle., 28(17), 1570-1575.
https://doi.org/10.1089/ars.2017.7433

Opačić M, Stević ZD, Baščarević V, Zivić M, Spasić M, Spasojević I. Can Oxidation-Reduction Potential of Cerebrospinal Fluid Be a Monitoring Biomarker in Amyotrophic Lateral Sclerosis?. in Antioxidants & Redox Signaling. 2018;28(17):1570-1575.
doi:10.1089/ars.2017.7433 .

Opačić, Miloš, Stević, Zorica D, Baščarević, Vladimir, Zivić, Miroslav, Spasić, Mihajlo, Spasojević, Ivan, "Can Oxidation-Reduction Potential of Cerebrospinal Fluid Be a Monitoring Biomarker in Amyotrophic Lateral Sclerosis?" in Antioxidants & Redox Signaling, 28, no. 17 (2018):1570-1575,
https://doi.org/10.1089/ars.2017.7433 . .

TY  - JOUR
AU  - Opačić, Miloš
AU  - Ristic, Aleksandar J
AU  - Savić, Danijela Z
AU  - Selih, Vid Simon
AU  - Zivin, Marko
AU  - Sokic, Dragoslav
AU  - Raicević, Savo
AU  - Baščarević, Vladimir
AU  - Spasojević, Ivan
PY  - 2017
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/1080
AB  - The loss of metal homeostasis has been implicated in the pathophysiology of mesial temporal lobe epilepsy associated with hippocampal sclerosis (mTLE-HS). Here we applied laser ablation inductively coupled plasma mass spectrometry imaging to establish the spatial distribution of Zn, Fe, Cu and Mn in coronal sections of hippocampi of four patients with drug-resistant mTLE-HS who underwent amygdalohippocampectomy. Detailed maps of the metal concentrations in the different morphological areas/layers were built and analyzed. The highest level of Zn (>20 mu g g(-1)) was found in mossy fiber-rich regions -cornu ammonis field 4 (CA4), gyrus dentatus, and CA3. The distribution of Fe appears to reflect the routes of the main intrahippocampal blood vessels. The highest concentrations of Cu (410 mg g(-1)) and Mn (415 mu g g(-1)) were observed in regions/layers with neuron somata - subiculum, CA4, gyrus dentatus, and stratum pyramidale (SPy) in CA1 and CA2. Alveus and other regions with axons and dendrites generally showed lower levels of Zn, Cu, and Mn. The Cu concentration was decreased in the areas of total neuronal loss in SPy in CA1 (9.73 +/- 0.91 mu g g(-1)), compared to the subiculum (13.32 +/- .29 mu g g(-1); p = 0.043). The Cu and Mn concentrations correlated positively with neuron density in the SPy in CA1 (R = 0.629, p o 0.001; and R = 0.391, p = 0.004). These results provide a deeper insight into hippocampal metabolism of metals, and pave the road for identifying the components of the mechanism of epileptogenesis among Cu and Mn transporters and metalloproteins.
PB  - Royal Soc Chemistry, Cambridge
T2  - Metallomics
T1  - Metal maps of sclerotic hippocampi of patients with mesial temporal lobe epilepsy
EP  - 148
IS  - 2
SP  - 141
VL  - 9
DO  - 10.1039/c6mt00293e
ER  - 

@article{
author = "Opačić, Miloš and Ristic, Aleksandar J and Savić, Danijela Z and Selih, Vid Simon and Zivin, Marko and Sokic, Dragoslav and Raicević, Savo and Baščarević, Vladimir and Spasojević, Ivan",
year = "2017",
abstract = "The loss of metal homeostasis has been implicated in the pathophysiology of mesial temporal lobe epilepsy associated with hippocampal sclerosis (mTLE-HS). Here we applied laser ablation inductively coupled plasma mass spectrometry imaging to establish the spatial distribution of Zn, Fe, Cu and Mn in coronal sections of hippocampi of four patients with drug-resistant mTLE-HS who underwent amygdalohippocampectomy. Detailed maps of the metal concentrations in the different morphological areas/layers were built and analyzed. The highest level of Zn (>20 mu g g(-1)) was found in mossy fiber-rich regions -cornu ammonis field 4 (CA4), gyrus dentatus, and CA3. The distribution of Fe appears to reflect the routes of the main intrahippocampal blood vessels. The highest concentrations of Cu (410 mg g(-1)) and Mn (415 mu g g(-1)) were observed in regions/layers with neuron somata - subiculum, CA4, gyrus dentatus, and stratum pyramidale (SPy) in CA1 and CA2. Alveus and other regions with axons and dendrites generally showed lower levels of Zn, Cu, and Mn. The Cu concentration was decreased in the areas of total neuronal loss in SPy in CA1 (9.73 +/- 0.91 mu g g(-1)), compared to the subiculum (13.32 +/- .29 mu g g(-1); p = 0.043). The Cu and Mn concentrations correlated positively with neuron density in the SPy in CA1 (R = 0.629, p o 0.001; and R = 0.391, p = 0.004). These results provide a deeper insight into hippocampal metabolism of metals, and pave the road for identifying the components of the mechanism of epileptogenesis among Cu and Mn transporters and metalloproteins.",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "Metallomics",
title = "Metal maps of sclerotic hippocampi of patients with mesial temporal lobe epilepsy",
pages = "148-141",
number = "2",
volume = "9",
doi = "10.1039/c6mt00293e"
}

Opačić, M., Ristic, A. J., Savić, D. Z., Selih, V. S., Zivin, M., Sokic, D., Raicević, S., Baščarević, V.,& Spasojević, I.. (2017). Metal maps of sclerotic hippocampi of patients with mesial temporal lobe epilepsy. in Metallomics
Royal Soc Chemistry, Cambridge., 9(2), 141-148.
https://doi.org/10.1039/c6mt00293e

Opačić M, Ristic AJ, Savić DZ, Selih VS, Zivin M, Sokic D, Raicević S, Baščarević V, Spasojević I. Metal maps of sclerotic hippocampi of patients with mesial temporal lobe epilepsy. in Metallomics. 2017;9(2):141-148.
doi:10.1039/c6mt00293e .

Opačić, Miloš, Ristic, Aleksandar J, Savić, Danijela Z, Selih, Vid Simon, Zivin, Marko, Sokic, Dragoslav, Raicević, Savo, Baščarević, Vladimir, Spasojević, Ivan, "Metal maps of sclerotic hippocampi of patients with mesial temporal lobe epilepsy" in Metallomics, 9, no. 2 (2017):141-148,
https://doi.org/10.1039/c6mt00293e . .

TY  - JOUR
AU  - Kalauzi, Aleksandar
AU  - Nikolić, Ljiljana M.
AU  - Savić, Danijela Z
AU  - Radotić, Ksenija
PY  - 2015
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/897
AB  - The physiological and biochemical factors that lead to cell death have not been recognized completely. To our knowledge, there are no data on the bioelectric parameters that characterize early period of cell death, as well as on the appearance of related membrane current frequencies. We studied early parameters of glutaraldehyde (GA)-induced cell death, by examining the membrane properties of mouse microglia using the whole-cell patch-clamp technique. In addition, we investigated the GA-induced changes in the membrane current frequency, to see if characteristic frequencies would appear in dying cell. For data analysis, we applied a new approach, an improved multiple moving window length analysis and interval weighted spectra averaging (IWSA). We chose GA for its ability to induce almost instantaneous cell death. The 0.6 % GA did not induce changes in the bioelectric membrane properties of microglia. However, the 3 % GA caused significant decrease of membrane capacitance and resistance accompanied by the prominent increase in the membrane currents and nearly ohmic current response of microglial cells. These data indicate that 3 % GA caused complete loss of the membrane function consequently inducing instantaneous cell death. The membrane function loss was characterized by appearance of the 1.26-4.62 Hz frequency peak in the IWSA spectra, while no significant increase of amplitudes could be observed for cells treated with 0.6 % GA. To our knowledge, this is the first record of a frequency associated with complete loss of the membrane function and thus can be considered as an early indicator of cell death.
PB  - Springer, New York
T2  - Journal of Membrane Biology
T1  - Cell Death Parameters as Revealed by Whole-Cell Patch-Clamp and Interval Weighted Spectra Averaging: Changes in Membrane Properties and Current Frequency of Cultured Mouse Microglial Cells Induced by Glutaraldehyde
EP  - 123
IS  - 1
SP  - 117
VL  - 248
DO  - 10.1007/s00232-014-9748-7
ER  - 

@article{
author = "Kalauzi, Aleksandar and Nikolić, Ljiljana M. and Savić, Danijela Z and Radotić, Ksenija",
year = "2015",
abstract = "The physiological and biochemical factors that lead to cell death have not been recognized completely. To our knowledge, there are no data on the bioelectric parameters that characterize early period of cell death, as well as on the appearance of related membrane current frequencies. We studied early parameters of glutaraldehyde (GA)-induced cell death, by examining the membrane properties of mouse microglia using the whole-cell patch-clamp technique. In addition, we investigated the GA-induced changes in the membrane current frequency, to see if characteristic frequencies would appear in dying cell. For data analysis, we applied a new approach, an improved multiple moving window length analysis and interval weighted spectra averaging (IWSA). We chose GA for its ability to induce almost instantaneous cell death. The 0.6 % GA did not induce changes in the bioelectric membrane properties of microglia. However, the 3 % GA caused significant decrease of membrane capacitance and resistance accompanied by the prominent increase in the membrane currents and nearly ohmic current response of microglial cells. These data indicate that 3 % GA caused complete loss of the membrane function consequently inducing instantaneous cell death. The membrane function loss was characterized by appearance of the 1.26-4.62 Hz frequency peak in the IWSA spectra, while no significant increase of amplitudes could be observed for cells treated with 0.6 % GA. To our knowledge, this is the first record of a frequency associated with complete loss of the membrane function and thus can be considered as an early indicator of cell death.",
publisher = "Springer, New York",
journal = "Journal of Membrane Biology",
title = "Cell Death Parameters as Revealed by Whole-Cell Patch-Clamp and Interval Weighted Spectra Averaging: Changes in Membrane Properties and Current Frequency of Cultured Mouse Microglial Cells Induced by Glutaraldehyde",
pages = "123-117",
number = "1",
volume = "248",
doi = "10.1007/s00232-014-9748-7"
}

Kalauzi, A., Nikolić, L. M., Savić, D. Z.,& Radotić, K.. (2015). Cell Death Parameters as Revealed by Whole-Cell Patch-Clamp and Interval Weighted Spectra Averaging: Changes in Membrane Properties and Current Frequency of Cultured Mouse Microglial Cells Induced by Glutaraldehyde. in Journal of Membrane Biology
Springer, New York., 248(1), 117-123.
https://doi.org/10.1007/s00232-014-9748-7

Kalauzi A, Nikolić LM, Savić DZ, Radotić K. Cell Death Parameters as Revealed by Whole-Cell Patch-Clamp and Interval Weighted Spectra Averaging: Changes in Membrane Properties and Current Frequency of Cultured Mouse Microglial Cells Induced by Glutaraldehyde. in Journal of Membrane Biology. 2015;248(1):117-123.
doi:10.1007/s00232-014-9748-7 .

Kalauzi, Aleksandar, Nikolić, Ljiljana M., Savić, Danijela Z, Radotić, Ksenija, "Cell Death Parameters as Revealed by Whole-Cell Patch-Clamp and Interval Weighted Spectra Averaging: Changes in Membrane Properties and Current Frequency of Cultured Mouse Microglial Cells Induced by Glutaraldehyde" in Journal of Membrane Biology, 248, no. 1 (2015):117-123,
https://doi.org/10.1007/s00232-014-9748-7 . .

TY  - JOUR
AU  - Ristic, Aleksandar J
AU  - Savić, Danijela Z
AU  - Sokic, Dragoslav
AU  - Bogdanović Pristov, Jelena
AU  - Nestorov, Jelena
AU  - Baščarević, Vladimir
AU  - Raicević, Savo
AU  - Savić, Slobodan
AU  - Spasojević, Ivan
PY  - 2015
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/898
AB  - ObjectiveTo examine antioxidative system in hippocampi of patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis (mTLE-HS). MethodsActivity and levels of antioxidative enzymescatalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), manganese superoxide dismutase (MnSOD), and copper-zinc superoxide dismutase (CuZnSOD)were assessed in hippocampi of nine pharmacoresistant mTLE-HS patients (mean age 37.7[standard deviation] 6.6years) who underwent amygdalohippocampectomy, and in 10 hippocampi obtained via autopsy from five neurologically intact controls (mean age 34.49.0years). Subfield and cellular (neuron/astrocyte) distribution of CAT, GPx, and MnSOD was analyzed in detail using immunohistochemical staining. ResultsSclerotic hippocampi showed drastically increased activity of hydrogen peroxide-removing enzymes, CAT (p lt 0.001), GPx (p lt 0.001), and GR (p lt 0.001), and significantly higher protein levels of CAT (p=0.006), GPx (p=0.040), GR (p=0.024), and MnSOD (p=0.004), compared to controls. CAT immunofluorescence was located mainly in neurons in both controls and HS. Control hippocampi showed GPx staining in blood vessels and CA neurons. In HS, GPx-rich loci, representing bundles of astrocytes, emerged in different hippocampal regions, whereas the number of GPx-positive vessels was drastically decreased. Neurons with abnormal morphology and strong MnSOD immunofluorescence were present in all neuronal layers in HS. Small autofluorescent deposits, most likely lipofuscin, were observed, along with astrogliosis, in CA1 in HS. SignificanceAntioxidative system is upregulated in HS. This documents, for the first time, that epileptogenic hippocampi are exposed to oxidative stress. Our findings provide a basis for understanding the potential involvement of redox alterations in the pathology of epilepsy, and may open new pharmacologic perspectives for mTLE-HS treatment.
PB  - Wiley, Hoboken
T2  - Epilepsia
T1  - Hippocampal antioxidative system in mesial temporal lobe epilepsy
EP  - 799
IS  - 5
SP  - 789
VL  - 56
DO  - 10.1111/epi.12981
ER  - 

@article{
author = "Ristic, Aleksandar J and Savić, Danijela Z and Sokic, Dragoslav and Bogdanović Pristov, Jelena and Nestorov, Jelena and Baščarević, Vladimir and Raicević, Savo and Savić, Slobodan and Spasojević, Ivan",
year = "2015",
abstract = "ObjectiveTo examine antioxidative system in hippocampi of patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis (mTLE-HS). MethodsActivity and levels of antioxidative enzymescatalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), manganese superoxide dismutase (MnSOD), and copper-zinc superoxide dismutase (CuZnSOD)were assessed in hippocampi of nine pharmacoresistant mTLE-HS patients (mean age 37.7[standard deviation] 6.6years) who underwent amygdalohippocampectomy, and in 10 hippocampi obtained via autopsy from five neurologically intact controls (mean age 34.49.0years). Subfield and cellular (neuron/astrocyte) distribution of CAT, GPx, and MnSOD was analyzed in detail using immunohistochemical staining. ResultsSclerotic hippocampi showed drastically increased activity of hydrogen peroxide-removing enzymes, CAT (p lt 0.001), GPx (p lt 0.001), and GR (p lt 0.001), and significantly higher protein levels of CAT (p=0.006), GPx (p=0.040), GR (p=0.024), and MnSOD (p=0.004), compared to controls. CAT immunofluorescence was located mainly in neurons in both controls and HS. Control hippocampi showed GPx staining in blood vessels and CA neurons. In HS, GPx-rich loci, representing bundles of astrocytes, emerged in different hippocampal regions, whereas the number of GPx-positive vessels was drastically decreased. Neurons with abnormal morphology and strong MnSOD immunofluorescence were present in all neuronal layers in HS. Small autofluorescent deposits, most likely lipofuscin, were observed, along with astrogliosis, in CA1 in HS. SignificanceAntioxidative system is upregulated in HS. This documents, for the first time, that epileptogenic hippocampi are exposed to oxidative stress. Our findings provide a basis for understanding the potential involvement of redox alterations in the pathology of epilepsy, and may open new pharmacologic perspectives for mTLE-HS treatment.",
publisher = "Wiley, Hoboken",
journal = "Epilepsia",
title = "Hippocampal antioxidative system in mesial temporal lobe epilepsy",
pages = "799-789",
number = "5",
volume = "56",
doi = "10.1111/epi.12981"
}

Ristic, A. J., Savić, D. Z., Sokic, D., Bogdanović Pristov, J., Nestorov, J., Baščarević, V., Raicević, S., Savić, S.,& Spasojević, I.. (2015). Hippocampal antioxidative system in mesial temporal lobe epilepsy. in Epilepsia
Wiley, Hoboken., 56(5), 789-799.
https://doi.org/10.1111/epi.12981

Ristic AJ, Savić DZ, Sokic D, Bogdanović Pristov J, Nestorov J, Baščarević V, Raicević S, Savić S, Spasojević I. Hippocampal antioxidative system in mesial temporal lobe epilepsy. in Epilepsia. 2015;56(5):789-799.
doi:10.1111/epi.12981 .

Ristic, Aleksandar J, Savić, Danijela Z, Sokic, Dragoslav, Bogdanović Pristov, Jelena, Nestorov, Jelena, Baščarević, Vladimir, Raicević, Savo, Savić, Slobodan, Spasojević, Ivan, "Hippocampal antioxidative system in mesial temporal lobe epilepsy" in Epilepsia, 56, no. 5 (2015):789-799,
https://doi.org/10.1111/epi.12981 . .

TY  - JOUR
AU  - Bajić, Aleksandar
AU  - Spasić, Mihajlo
AU  - Andjus, Pavle R
AU  - Savić, Danijela Z
AU  - Parabucki, Ana B
AU  - Nikolić-Kokić, Aleksandra
AU  - Spasojević, Ivan
PY  - 2013
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/707
AB  - The effects of H2O2 are widely studied in cell cultures and other in vitro systems. However, such investigations are performed with the assumption that H2O2 concentration is constant, which may not properly reflect in vivo settings, particularly in redox-turbulent microenvironments such as mitochondria. Here we introduced and tested a novel concept of fluctuating oxidative stress. We treated C6 astroglial cells and primary astrocytes with H2O2, using three regimes of exposure - continuous, as well as fluctuating at low or high rate, and evaluated mitochondrial membrane potential and other parameters of mitochondrial activity - respiration, reducing capacity, and superoxide production, as well as intracellular ATP, intracellular calcium, and NF-kappa B activation. When compared to continuous exposure, fluctuating H2O2 induced a pronounced hyperpolarization in mitochondria, whereas the activity of electron transport chain appears not to be significantly affected. H2O2 provoked a decrease of ATP level and an increase of intracellular calcium concentration, independently of the regime of treatment. However, fluctuating H2O2 induced a specific pattern of large-amplitude fluctuations of calcium concentration. An impact on NF kappa B activation was observed for high rate fluctuations, whereas continuous and low rate fluctuating oxidative stress did not provoke significant effects. Presented results outline the (patho)physiological relevance of redox fluctuations.
PB  - Public Library Science, San Francisco
T2  - PLoS One
T1  - Fluctuating vs. Continuous Exposure to H2O2: The Effects on Mitochondrial Membrane Potential, Intracellular Calcium, and NF-kappa B in Astroglia
IS  - 10
VL  - 8
DO  - 10.1371/journal.pone.0076383
ER  - 

@article{
author = "Bajić, Aleksandar and Spasić, Mihajlo and Andjus, Pavle R and Savić, Danijela Z and Parabucki, Ana B and Nikolić-Kokić, Aleksandra and Spasojević, Ivan",
year = "2013",
abstract = "The effects of H2O2 are widely studied in cell cultures and other in vitro systems. However, such investigations are performed with the assumption that H2O2 concentration is constant, which may not properly reflect in vivo settings, particularly in redox-turbulent microenvironments such as mitochondria. Here we introduced and tested a novel concept of fluctuating oxidative stress. We treated C6 astroglial cells and primary astrocytes with H2O2, using three regimes of exposure - continuous, as well as fluctuating at low or high rate, and evaluated mitochondrial membrane potential and other parameters of mitochondrial activity - respiration, reducing capacity, and superoxide production, as well as intracellular ATP, intracellular calcium, and NF-kappa B activation. When compared to continuous exposure, fluctuating H2O2 induced a pronounced hyperpolarization in mitochondria, whereas the activity of electron transport chain appears not to be significantly affected. H2O2 provoked a decrease of ATP level and an increase of intracellular calcium concentration, independently of the regime of treatment. However, fluctuating H2O2 induced a specific pattern of large-amplitude fluctuations of calcium concentration. An impact on NF kappa B activation was observed for high rate fluctuations, whereas continuous and low rate fluctuating oxidative stress did not provoke significant effects. Presented results outline the (patho)physiological relevance of redox fluctuations.",
publisher = "Public Library Science, San Francisco",
journal = "PLoS One",
title = "Fluctuating vs. Continuous Exposure to H2O2: The Effects on Mitochondrial Membrane Potential, Intracellular Calcium, and NF-kappa B in Astroglia",
number = "10",
volume = "8",
doi = "10.1371/journal.pone.0076383"
}

Bajić, A., Spasić, M., Andjus, P. R., Savić, D. Z., Parabucki, A. B., Nikolić-Kokić, A.,& Spasojević, I.. (2013). Fluctuating vs. Continuous Exposure to H2O2: The Effects on Mitochondrial Membrane Potential, Intracellular Calcium, and NF-kappa B in Astroglia. in PLoS One
Public Library Science, San Francisco., 8(10).
https://doi.org/10.1371/journal.pone.0076383

Bajić A, Spasić M, Andjus PR, Savić DZ, Parabucki AB, Nikolić-Kokić A, Spasojević I. Fluctuating vs. Continuous Exposure to H2O2: The Effects on Mitochondrial Membrane Potential, Intracellular Calcium, and NF-kappa B in Astroglia. in PLoS One. 2013;8(10).
doi:10.1371/journal.pone.0076383 .

Bajić, Aleksandar, Spasić, Mihajlo, Andjus, Pavle R, Savić, Danijela Z, Parabucki, Ana B, Nikolić-Kokić, Aleksandra, Spasojević, Ivan, "Fluctuating vs. Continuous Exposure to H2O2: The Effects on Mitochondrial Membrane Potential, Intracellular Calcium, and NF-kappa B in Astroglia" in PLoS One, 8, no. 10 (2013),
https://doi.org/10.1371/journal.pone.0076383 . .