Neuropharmacology and analgesiaProtection by taurine of rat brain cortical slices against oxygen glucose deprivation- and reoxygenation-induced damage
Introduction
Excitatory amino acids are massively released from neurons during hypoxia and ischemia both in vitro (Pellegrini-Giampietro et al., 1990, Collard and Menon-Johansson, 1993, Nelson et al., 2003) and in vivo (Hagberg et al., 1985, Globus et al., 1988, Takagi et al., 1993) and overstimulation of their receptors leads to neuronal death (for a review see Bano and Nicotera (2007)). Other critical pathophysiological processes that contribute to cell injury in ischemic stroke include formation of ionic- as well as vasogenic-edema (Simard et al., 2007a). Molecular mechanisms involved in these processes are only beginning to be elucidated although those largely independent of continuous expenditure of energy such as the activity of nonselective cation channels are likely to be markedly involved (Simard et al., 2007a, Simard et al., 2007b, Inoue and Okada, 2007).
Taurine (2-aminoethanesulphonic acid), one of the most abundant free amino acids in the central nervous system, is released in high concentrations from brain cells under a variety of damaging conditions, including osmotic imbalance, ischemia or hypoxia (Saransaari and Oja, 1999, Saransaari and Oja, 2007, Ritz et al., 2006, Shennan, 2008) exposure to hot environment and fever (Frosini, 2007). In the case of ischemia, the release occurs simultaneously with the ischemic-induced raise of excitatory amino acid levels, and this might represent an important protective mechanism against excitotoxicity, counteracting the harmful effects which lead to neuronal death (Saransaari and Oja, 2007, Saransaari and Oja, 2000, Oja and Saransaari, 2000). Furthermore, it has been demonstrated that taurine-containing neurons are fairly resistant to cerebral ischemia induced by four-vessel occlusion in rats (Matsumoto et al., 1991, Wu et al., 1994) and that this amino acid protects rat cerebellar granule cells exposed to kainate without affecting the production of reactive oxygen species (Boldyrev et al., 1999). However, the mechanism of neuroprotection has not been so far clarified, and the exact molecular target or signal chain activated by taurine remains unknown. It has been demonstrated that taurine interferes with the function of GABA and glycine receptors (Kontro and Oja, 1987a, Frosini et al., 2003a) and a putative specific taurine recognition site has been described (Frosini et al., 2003a, Kontro and Oja, 1987b, Frosini et al., 2003b). However, whether the protective effect of taurine is mediated by GABA receptors or by intracellular mechanisms during excitotoxic-induced brain injury remains unresolved.
The aim of the present investigation was to assess whether taurine could prevent or counteract neuronal injury induced by oxygen/glucose deprivation and reperfusion, in rat brain cortical slices. Tissue damage and protection were assessed by measuring the release of glutamate and lactate dehydrogenase (LDH) into bathing artificial cerebrospinal fluid (aCSF) during reperfusion and by determining at the end of the experiment tissue water gain taken as an index of tissue edema (Hrabetová et al., 2002, MacGregor et al., 2003). Results demonstrated that taurine could fully antagonise oxygen/glucose deprivation and reperfusion-induced edema. This effect was dependent on taurine transport into the cells as well as on GABAA receptor activation and involved the activity of volume-sensitive outwardly rectifying (VSOR) Cl− channels.
Section snippets
Compounds
GABA, Trizma® base, ascorbic acid, sodium pyruvate, β-nicotinamide adenine dinucleotide (NAD+), β-nicotinamide adenine dinucleotide reduced form (NADH), glutamate, glutamate dehydrogenase (GDH), taurine, glutamate, bicuculline methyl-chloride, 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), bovine serum albumine (BSA) and all artificial cerebrospinal fluid components were acquired from Sigma-Aldrich Co. (St Louis, MO, U.S.A.).
2-(Guanidino)ethanesulphonic acid (GES) was prepared by the
Effect of taurine added during the reperfusion phase on oxygen glucose deprivation- and reperfusion-induced injury in rat brain cortical slices
Rat cortical slices incubated in aCSF for 120 min (control conditions) released into the reoxygenation medium 0.31 ± 0.02 nmol/mg wet tissue (n = 8) and 2.42 ± 0.18 U/mg protein (n = 19) of glutamate and LDH, respectively, while tissue water content was 9.92 ± 0.40 gH2O/g tissue dry weight.
30 min oxygen/glucose deprivation, followed by 90 min of reperfusion, induced a significant efflux of LDH and glutamate which amounted to 9.31 ± 0.48 U/mg wet tissue (P < 0.001 vs control, n = 18) and to 0.7 ± 0.03 nmol/mg wet
Discussion
In the present study the potential neuroprotective effects of taurine in an in vitro experimental model of brain ischemia and reperfusion has been investigated. Studies performed so far have reported mostly the protection afforded by taurine when administered before the exposure of brain tissues to a variety of cell-damaging conditions and little information is available concerning its possible therapeutic usefulness in cerebral stroke. The protective efficacy of taurine has been assessed in
Acknowledgments
This work was financed by PAR and MIUR funds.
References (62)
- et al.
Carnosine and taurine protect rat cerebellar granular cells from free radical damage
Neurosci. Lett.
(1999) - et al.
Taurine activates GABAA but not GABAB receptors in rat hippocampal CA1 area
Brain Res.
(2000) Changes in CSF composition during heat stress and fever in conscious rabbits
Prog. Brain Res.
(2007)- et al.
Co-operativity in sodium-independent taurine binding to brain membranes in the mouse
Neuroscience
(1987) - et al.
Ischemic neuronal injury in the rat hippocampus following transient forebrain ischemia: evaluation using in vivo microdialysis
Brain Res.
(1991) - et al.
Pharmacology of ischemia-induced glutamate efflux from rat cerebral cortex in vitro
Brain Res.
(2003) - et al.
Modulation of taurine release by glutamate receptors and nitric oxide
Prog. Neurobiol.
(2000) - et al.
Neuroprotection afforded by diazepam against oxygen/glucose deprivation-induced injury in rat cortical brain slices
Eur. J. Pharmacol.
(2007) Ischemic brain edema
Prog. Cariovasc. Dis.
(1999)- et al.
Characteristics of ischemia-induced taurine release in the developing mouse hippocampus
Neuroscience
(1999)
Expression and function of glycine receptors in striatal cholinergic interneurons from rat and mouse
Neuroscience
Intracellular calcium redistribution accompanies changes in total tissue Na+, K+ and water during the first two hours of in vitro incubation of hippocampal slices
Neuroscience
Brain oedema in focal ischaemia: molecular pathophysiology and theoretical implications
Lancet Neurol.
Non-selective cation channels, transient receptor potential channels and ischemic stroke
Biochim. Biophys. Acta.
Neuroprotective effect of taurine against focal cerebral ischemia in rats possibly mediated by activation of both GABAA and glycine receptors
Neuropharmacology
Taurine inhibits rat substantia nigra pars reticulata neurons by activation of GABA- and glycine-linked chloride conductance
Brain Res.
Excitotoxic mechanism of cell swelling in rat cerebral cortical slices treated acutely with ammonia
Neurochem. Int.
Sequential release of GABA by exocytosis and reversed uptake leads to neuronal swelling in simulated ischemia of hippocampal slices
J. Neurosci.
Ca2+ signals and neuronal death in brain ischemia
Stroke
Mechanisms and timing of deaths from cerebral infarction
Stroke
Ascorbate inhibits edema in brain slices
J. Neurochem.
GABAA receptor subtypes: ligand binding heterogeneity demonstrated by photoaffinity labeling and autoradiography
J. Neurochem.
Long-lasting enhancement of corticostriatal neurotransmission by taurine
Eur. J. Neurosci.
Effects of short-term hypoxia on [3H]glutamate release from preloaded hippocampal and cortical synaptosomes
Neurochem. Res.
Extracellular volume decreases while cell volume is maintained by ion uptake in rat brain during acute hypernatremia
J. Physiol.
Neurological deterioration in acute ischemic stroke: potential predictors and associated factors in the European cooperative acute stroke study (ECASS) I
Stroke
Recombinant GABAA receptor desensitization: the role of the gamma 2 subunit and its physiological significance
J. Physiol.
Different effects of volatile anaesthetics and polyhalogenated alkanes on depolarization-evoked glutamate release in rat cortical brain slices
Anesth. Analg.
Taurine increases mitochondrial buffering of calcium: role in neuroprotection
Amino Acids
The role of taurine in the central nervous system and the modulation of intracellular calcium homeostasis
Neurochem. Res.
Interactions of taurine and structurally related analogues with the GABAergic system and taurine binding sites of rabbit brain
Br. J. Pharmacol.
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