title: Hippocampal antioxidative system in mesial temporal lobe epilepsy.
abstract: OBJECTIVE
  To examine antioxidative system in hippocampi of patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis (mTLE-HS).
  
  
  METHODS
  Activity and levels of antioxidative enzymes-catalase (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] 6.6 years) who underwent amygdalohippocampectomy, and in 10 hippocampi obtained via autopsy from five neurologically intact controls (mean age 34.4 ± 9.0 years). Subfield and cellular (neuron/astrocyte) distribution of CAT, GPx, and MnSOD was analyzed in detail using immunohistochemical staining.
  
  
  RESULTS
  Sclerotic hippocampi showed drastically increased activity of hydrogen peroxide-removing enzymes, CAT (p < 0.001), GPx (p < 0.001), and GR (p < 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.
  
  
  CONCLUSIONS
  Antioxidative 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.
authors: Center for Epilepsy and Sleep Disorders, Neurology Clinic, Clinical Center of Serbia, Belgrade, Serbia.
authors: Aleksandar J
authors: AJ
authors: Ristić
authors: Department of Neurobiology, Institute for Biological Research "Siniša Stanković", University of Belgrade, Belgrade, Serbia.
authors: Danijela
authors: D
authors: Savić
authors: Center for Epilepsy and Sleep Disorders, Neurology Clinic, Clinical Center of Serbia, Belgrade, Serbia.
authors: Dragoslav
authors: D
authors: Sokić
authors: Life Sciences Department, Institute for Multidisciplinary Research, University of Belgrade, Belgrade, Serbia.
authors: Jelena
authors: J
authors: Bogdanović Pristov
authors: Department of Biochemistry, Institute for Biological Research "Siniša Stanković", University of Belgrade, Belgrade, Serbia.
authors: Jelena
authors: J
authors: Nestorov
authors: Institute for Neurosurgery, Clinical Center of Serbia, Belgrade, Serbia.
authors: Vladimir
authors: V
authors: Baščarević
authors: Institute for Neurosurgery, Clinical Center of Serbia, Belgrade, Serbia.
authors: Savo
authors: S
authors: Raičević
authors: Institute of Forensic Medicine, Medical School, University of Belgrade, Belgrade, Serbia.
authors: Slobodan
authors: S
authors: Savić
authors: Life Sciences Department, Institute for Multidisciplinary Research, University of Belgrade, Belgrade, Serbia.
authors: Ivan
authors: I
authors: Spasojević
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004833:Epilepsy, Temporal Lobe / Q000150:complications / Q000473:pathology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D008297:Male; D010088:Oxidoreductases / Q000378:metabolism*; D012598:Sclerosis / Q000209:etiology; D013053:Spectrophotometry; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D005904:Glial Fibrillary Acidic Protein; D010088:Oxidoreductases
keywords: Catalase; Glutathione peroxidase; Hippocampal sclerosis; Mesial temporal epilepsy; Mitochondria; Superoxide dismutase