Hippocampal antioxidative system in mesial temporal lobe epilepsy
Samo za registrovane korisnike
2015
Autori
Ristic, Aleksandar JSavić, Danijela Z
Sokic, Dragoslav
Bogdanović Pristov, Jelena
Nestorov, Jelena
Baščarević, Vladimir
Raicević, Savo
Savić, Slobodan
Spasojević, Ivan
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
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.
Ključne reči:
Superoxide dismutase / Mitochondria / Mesial temporal epilepsy / Hippocampal sclerosis / Glutathione peroxidase / CatalaseIzvor:
Epilepsia, 2015, 56, 5, 789-799Izdavač:
- Wiley, Hoboken
Finansiranje / projekti:
- Ćelijska i molekulska osnova neuroinflamacije: potencijala ciljna mesta za translacionu medicinu i terapiju (RS-41014)
- Molekularni mehanizmi redoks signalinga u homeostazi, adaptaciji i patologiji (RS-173014)
DOI: 10.1111/epi.12981
ISSN: 0013-9580
PubMed: 25864570
WoS: 000354641700021
Scopus: 2-s2.0-84929508257
Institucija/grupa
Institut za multidisciplinarna istraživanjaTY - 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 . .