Transient in vivo membrane depolarization and glutamate release before anoxic depolarization in rat striatum

Increased extracellular glutamate ([GLU]e), under the condition of cerebral ischemia, anoxia or hypoxia, has been recognized as being associated with neuronal cell damage and death. We performed real-time monitoring of [GLU]e dynamics in vivo in the rat striatum during systemic acute anoxia or hypox ia, as well as monitoring the direct current potential (DC) and cerebral bl ood flow (CBF). Adult Wistar rats were orotracheally intubated and artifici ally ventilated with room air. A microdialysis electrode, temperature senso r probe, DC microelectrode and laser Doppler probe were then implanted. The inspired gas was changed to 100% N-2 (anoxia), or to 3, 5 or 8% O-2 (remai nder N-2) (hypoxia). With 100% N-2, distinct biphasic [GLU]e elevations wer e observed. With 3% O-2, a transient [GLU]e increase was seen before anoxic depolarization (AD). With 5% O-2, however. the start of the transient [GLU ]e increase was significantly delayed. Anoxia-induced depolarization starte d at about 100 s. The 3% O-2-induced transient depolarization and AD began at nearly the same time as the transient and AD-induced increase in [GLU]e. Similarly, the responses to 5% O-2 showed significant delays in the transi ent depolarization and AD-induced increase in [GLU]e. CBF during 3 or 5% O- 2 hypoxic insult was consistently maintained above the control level, i.e., prior to cardiac arrest. Our new dialysis electrode method employing both GOX and ferrocene-conjugated bovine serum albumin allowed evaluation of tra nsient [GLU]e dynamics in the early phase of severe hypoxia in vivo. (C) 19 99 Elsevier Science B.V. All rights reserved.