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Neuroprotective effects of ebselen following forebrain ischemia: involvement of glutamate and nitric oxide.
- Source :
-
Neurologia medico-chirurgica [Neurol Med Chir (Tokyo)] 2011; Vol. 51 (5), pp. 337-43. - Publication Year :
- 2011
-
Abstract
- Ebselen is a mimic of glutathione peroxidase that reacts with peroxynitrite and inhibits nitric oxide (NO) synthase. Ebselen has beneficial effects on the neurological outcome of patients with stroke. In this study, the mechanisms by which ebselen can elicit neuroprotective effects against ischemic brain injury were investigated in male Wistar rats. Experimental forebrain ischemia was induced by bilateral common carotid artery occlusion with hemorrhagic hypotension. Ebselen was administered to animals in the treatment group 2 hours prior to the induction of forebrain ischemia, and placebo was administered in the control group. Cerebral blood flow (CBF) was measured by the hydrogen clearance method. Cortical extracellular levels of excitatory amino acids (EAAs) and NO were evaluated using in vivo microdialysis. Neuronal damage in the CA1 subfield of the hippocampus was assessed in brains harvested after a 24-hour period of survival. CBF did not recover to normal physiological levels after ischemic insults in either the control or treatment groups. The differences in the sequential changes in extracellular EAA and NO levels between groups were not statistically significant. There was a significantly larger mean density of intact, undamaged neurons in the CA1 subfield in the treatment group than in the control group. The neuroprotective effects of ebselen were reflected in the histological findings, without significant inhibition of glutamate release or NO synthesis during the acute phase of experimentally induced cerebral ischemia.
- Subjects :
- Animals
Brain Ischemia drug therapy
CA1 Region, Hippocampal drug effects
Disease Models, Animal
Enzyme Inhibitors pharmacology
Glutamic Acid drug effects
Glutamic Acid metabolism
Isoindoles
Male
Microdialysis
Neurotransmitter Agents metabolism
Nitric Oxide Synthase drug effects
Presynaptic Terminals drug effects
Presynaptic Terminals metabolism
Prosencephalon
Random Allocation
Rats
Rats, Wistar
Azoles pharmacology
Brain Ischemia pathology
CA1 Region, Hippocampal pathology
Cerebrovascular Circulation drug effects
Neuroprotective Agents pharmacology
Nitric Oxide metabolism
Organoselenium Compounds pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1349-8029
- Volume :
- 51
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Neurologia medico-chirurgica
- Publication Type :
- Academic Journal
- Accession number :
- 21613757
- Full Text :
- https://doi.org/10.2176/nmc.51.337