Isoflurane preconditioning decreases glutamate receptor overactivation-induced Purkinje neuronal injury in rat cerebellar slices

A brain slice model was used to test the hypothesis that preconditioning with isoflurane, a commonly used volatile anesthetic in clinical practice, reduces neuronal injury caused by overstimulation of glutamate receptors. Glutamate receptors were stimulated by various concentrations of glutamate for...

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Veröffentlicht in:Brain research 2005-08, Vol.1054 (2), p.143-151
Hauptverfasser: Zheng, Shuqiu, Zuo, Zhiyi
Format: Artikel
Sprache:eng
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Zusammenfassung:A brain slice model was used to test the hypothesis that preconditioning with isoflurane, a commonly used volatile anesthetic in clinical practice, reduces neuronal injury caused by overstimulation of glutamate receptors. Glutamate receptors were stimulated by various concentrations of glutamate for 20 min, N-methyl- d-aspartate (NMDA) for 15 min or α-amino-3-hydroxy-5-methyl-4-isoxazol propionic acid (AMPA) for 15 min. Morphology of Purkinje neurons in the cerebellar slices of adult male Sprague–Dawley rats was evaluated 5 h after the agonist stimulation. Glutamate, NMDA and AMPA induced a dose-dependent decrease in the percentage of morphologically normal Purkinje neurons. The concentration to induce the maximal neurotoxic effect was 300 μM for glutamate, 300 μM for NMDA and 30 μM for AMPA. Isoflurane preconditioning (2% isoflurane for 30 min and then a 15-min rest period before the agonist stimulation) significantly reduced the neurotoxicity induced by 300 μM glutamate, 300 μM NMDA or 30 μM AMPA. Isoflurane preconditioning-induced protection against glutamate neurotoxicity was abolished by two protein kinase C (PKC) inhibitors, calphostin C (0.5 μM) and chelerythrine (5 μM), or a nitric oxide synthase (NOS) inhibitor, l-nitro G-arginine methyl ester ( l-NAME, 1.5 mM), but was not affected by an adenosine A1 receptor inhibitor, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 300 nM), or a Gi protein inhibitor, pertussis toxin (PTX, 200 ng/ml). Isoflurane preconditioning-induced protection against NMDA neurotoxicity was also abolished by calphostin C, chelerythrine or l-NAME. Thus, isoflurane preconditioning reduced glutamate receptor overstimulation-induced neuronal injury/death. This neuroprotection may be PKC- and NOS-dependent.
ISSN:0006-8993
1872-6240
DOI:10.1016/j.brainres.2005.06.064