Endothelin-triggered brain damage under hypoglycemia evidenced by real-time monitoring of dopamine release from rat striatal slices

Nebracetam (WEB 1881FU) Prevents N-Methyl-D-Aspartate Receptor-Mediated Neurotoxicity in Rat Striatal Slices

“…The present study demonstrated that the treatement with four reagents, L-glutamate, NMDA, BAY K-8644 and KCI during hypoglycemia/hypoxia enhanced the hypoglycemia/hypoxia-induced dopaminergic dysfunc tion, as observed in the case of treatment with high K+ and endothelin (2,3). An inappropriate influx of Ca 2+ leads to central neuron injury (1).…”

“…An inappropriate Ca 2+ entry in an etiological event of neuronal injury occurs largely through Ca 2+ channels gated by the N-methyl D-aspartate (NMDA) receptor, a subtype of glutamate receptor, but also through voltage-operated Ca 2+ chan nels (VOCC), Na+/Ca2+ exchangers and membrane leakage (1). We have shown that either high K+ or en dothelin participates in the development of hypoglycemia or hypoglycemia/hypoxia-induced brain damage through the VOCC in an in vitro model by directly monitoring the real-time dynamics of dopamine (DA) released from striatal slices (2,3). The striatum has been known to be highly vulnerable to hypoxia/ischemia (4) and contains NMDA receptors and 1,4-dihydropyridine binding sites labeling VOCC with a moderate density (5,6).…”

“…The 450-,um-thick striatal slices were prepared with a Mcllwain tissue chopper and mounted in the perfusion apparatus. The perfusion apparatus was fundamentally composed of a tissue perfusion component and an electrochemical de tector (ECD) monitoring component, as previously de scribed (2). In brief, the slice sandwiched between two membrane filters (3-,um pore size; Nuclepore, CA, U.S.A.) was placed in a chamber and perfused with ox ygenated (95% 02/5% CO2) Krebs-Ringer bicarbonate solution at pH 7.4, of the following composition: 118.0 mM NaCI, 4.7 mM KCI, 1.3 mM CaC12, 1.2 mM MgC12, 1.0 mM NaH2PO4, 25.0 mM NaHCO3 and 11.0 MM D-glucose, at a flow rate of 500 ,u 1/min at 37°C.…”

“…The experimental procedures are diagramed in Fig. 1 (2). Tissues were stimulated 3 times (S1 S3) at 20-min intervals by application of KCl (40 mM).…”

“…An inappropriate influx of Ca 2+ leads to central neuron injury (1). The hypoglycemia induced dopaminergic dysfunction was not enhanced by treatment with endothelin in the absence of external Ca 2+ during hypoglycemia (2). Thus, these four re agents appear to enhance the hypoglycemia/hypoxia induced damage of striatal dopaminergic neurons by in creasing intracellular Ca 2+ concentration, since these four reagents are accepted to activate the Ca 2+ chan nels (11).…”