title: Metal maps of sclerotic hippocampi of patients with mesial temporal lobe epilepsy.
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 μg 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 (>10 μg g-1) and Mn (>15 μg 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 μg g-1), compared to the subiculum (13.32 ± 1.29 μg g-1; p = 0.043). The Cu and Mn concentrations correlated positively with neuron density in the SPy in CA1 (R = 0.629, p < 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.
authors.affiliation: Life Sciences Department, Institute for Multidisciplinary Research, University of Belgrade, Kneza Višeslava 1, 11030 Belgrade, Serbia. redoxsci@gmail.com.
authors.forename: Miloš
authors.initials: M
authors.lastname: Opačić
authors.affiliation: Center for Epilepsy and Sleep Disorders, Neurology Clinic, Clinical Center of Serbia, Dr Subotića Starijeg 6, 11000 Belgrade, Serbia.
authors.forename: Aleksandar J
authors.initials: AJ
authors.lastname: Ristić
authors.affiliation: Department of Neurobiology, Institute for Biological Research 'Siniša Stanković', University of Belgrade, Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Danijela
authors.initials: D
authors.lastname: Savić
authors.affiliation: Department of Analytical Chemistry, National Institute of Chemistry Slovenia, Hajdrihova 19, SI-1001 Ljubljana, Slovenia.
authors.forename: Vid Simon
authors.initials: VS
authors.lastname: Šelih
authors.affiliation: Brain Research Laboratory, Institute of Pathophysiology, Medical Faculty, University of Ljubljana, Zaloška 4, 1000 Ljubljana, Slovenia.
authors.forename: Marko
authors.initials: M
authors.lastname: Živin
authors.affiliation: Center for Epilepsy and Sleep Disorders, Neurology Clinic, Clinical Center of Serbia, Dr Subotića Starijeg 6, 11000 Belgrade, Serbia.
authors.forename: Dragoslav
authors.initials: D
authors.lastname: Sokić
authors.affiliation: Neurosurgery Clinic, Clinical Center of Serbia, Koste Todorovića 4, 11000 Belgrade, Serbia.
authors.forename: Savo
authors.initials: S
authors.lastname: Raičević
authors.affiliation: Neurosurgery Clinic, Clinical Center of Serbia, Koste Todorovića 4, 11000 Belgrade, Serbia.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Baščarević
authors.affiliation: Life Sciences Department, Institute for Multidisciplinary Research, University of Belgrade, Kneza Višeslava 1, 11030 Belgrade, Serbia. redoxsci@gmail.com.
authors.forename: Ivan
authors.identifier: 0000-0002-3150-3087
authors.initials: I
authors.lastname: Spasojević
mesh_terms: D000328:Adult; D004833:Epilepsy, Temporal Lobe / Q000150:complications*; D005260:Female; D006179:Gyrus Cinguli / Q000378:metabolism / Q000473:pathology*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D008670:Metals / Q000032:analysis*; D012598:Sclerosis / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: D008670:Metals