TY  - JOUR
AU  - Röhnert, Peter
AU  - Schröder, Ulrich H
AU  - Ziabreva, Iryna
AU  - Täger, Michael
AU  - Reymann, Klaus G
AU  - Striggow, Frank
TI  - Insufficient endogenous redox buffer capacity may underlie neuronal vulnerability to cerebral ischemia and reperfusion.
JO  - Journal of neuroscience research
VL  - 90
IS  - 1
SN  - 0360-4012
CY  - New York, NY [u.a.]
PB  - Wiley-Liss
M1  - DZNE-2020-02698
SP  - 193-202
PY  - 2012
AB  - Reactive oxygen species (ROS) are key players in ischemia-induced neurodegeneration. We investigated whether hippocampal neurons may lack sufficient redox-buffering capacity to protect against ROS attacks. Using organotypic hippocampal slice cultures (OHSCs) transiently exposed to oxygen and glucose deprivation (OGD) and gerbils suffering from a two-vessel occlusion (2VO) as complementary ex vivo and in vivo models, we have elucidated whether the intrinsic redox systems interfere with ischemia-induced neurodegeneration. Cell- type-specific immunohistological staining of hippocampal slice cultures revealed that pyramidal neurons, in contrast to astrocytes and microglia, express free thiols only weakly. In addition, free thiol levels were extensively decreased throughout the hippocampal formation immediately after OGD, but recovered within 24 hr after reperfusion. In parallel, progressive glia activation and proliferation were observed. Increased neuronal exposure to ROS was monitored by dihydroethidium oxidation in hippocampal pyramidal cell layers immediately after OGD. Coadministration of reduction equivalents (α-lipoic acid) and thiol-stimulating agents (enalapril, ambroxol) decreased ischemia-induced neuronal damage in OGD-treated OHSCs and in gerbils exposed to 2VO, whereas single drug applications remained ineffective. In summary, limited redox buffering capacities of pyramidal neurons may underlie their exceptional vulnerability to cerebral ischemia. Consistently, multidrug treatments supporting endogenous redox systems may offer a strategy to promote valid neuroprotection.
KW  - Animals
KW  - Brain Ischemia: pathology
KW  - Cell Death
KW  - Disease Models, Animal
KW  - Ethidium: analogs & derivatives
KW  - Ethidium: metabolism
KW  - Fluoresceins: metabolism
KW  - Gerbillinae
KW  - Glial Fibrillary Acidic Protein: metabolism
KW  - Glucose: deficiency
KW  - Glycoproteins: metabolism
KW  - Hippocampus: cytology
KW  - Hypoxia
KW  - Lectins: metabolism
KW  - Neurons: drug effects
KW  - Neurons: metabolism
KW  - Neurons: pathology
KW  - Neuroprotective Agents: pharmacology
KW  - Organ Culture Techniques
KW  - Oxidation-Reduction
KW  - Rats
KW  - Rats, Wistar
KW  - Reactive Oxygen Species
KW  - Reperfusion Injury: pathology
KW  - Rhodamines: metabolism
KW  - Sulfhydryl Compounds: metabolism
KW  - Thioctic Acid: pharmacology
KW  - (((4-chloromethyl)benzoyl)amino)-tetramethylrhodamine (NLM Chemicals)
KW  - Fluoresceins (NLM Chemicals)
KW  - Glial Fibrillary Acidic Protein (NLM Chemicals)
KW  - Glycoproteins (NLM Chemicals)
KW  - Lectins (NLM Chemicals)
KW  - Neuroprotective Agents (NLM Chemicals)
KW  - Reactive Oxygen Species (NLM Chemicals)
KW  - Rhodamines (NLM Chemicals)
KW  - Sulfhydryl Compounds (NLM Chemicals)
KW  - isolectin B4-binding glycoprotein, rat (NLM Chemicals)
KW  - dihydroethidium (NLM Chemicals)
KW  - 5-chloromethylfluorescein (NLM Chemicals)
KW  - Thioctic Acid (NLM Chemicals)
KW  - Ethidium (NLM Chemicals)
KW  - Glucose (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:21971686
DO  - DOI:10.1002/jnr.22754
UR  - https://pub.dzne.de/record/136376
ER  -