Real-time measurement of ischemia-evoked glutamate release in the cerebral cortex of four and eleven vessel rat occlusion models

Interstitial levels of the neurotransmitter glutamate and cerebral blood flow changes were compared in two models of rat forebrain ischemia using the dialysis electrode technique and laser doppler flowmetry with brain temperature controlled. Ten-minute periods of cerebral ischemia were elicited by the four and an eleven vessel occlusion and compared to carotid artery transection. Elapsed time from the onset of ischemia to the ischemic plateau was 76.8 +/- 57.9 s in 4VO vs. 14.8 +/- 1.3 s in 11VO animals. Percent residual cerebral blood flow (CBF) was 13.5 +/- 8.8% during 4VO as opposed to 4.5 +/- 2.9% during 11VO, Concomitantly, cerebral glutamate levels rose to 255.7 +/- 72.8 mu mol l(-1) in the 4VO animals in comparison with levels of 138.5 +/- 78.7 and 135.7 +/- 40.2 mu mol l(-1) in the 11VO and carotid transection animals. During the first 89.6 +/- 47.4 s of reperfusion, glutamate levels rose to a second higher peak of 315.1 +/-179.2 mu mol l(-1) in 7 of 12 animals. Following reperfusion, glutamate levels in the 4VO and 11VO animals returned towards basal levels.This study demonstrates that 11VO causes a rapid drop in CBF to near zero levels, better mimicking complete forebrain ischemia than the traditional 4VO technique. Moreover, the 'low flow' state of cerebral ischemia, produced by traditional 4VO, results in a higher interstitial level of glutamate than a 'no flow' state, as exhibited by the 11VO technique. The dialysis electrode, used simultaneously with laser doppler flowmetry, real-time data acquisition, and continuous brain temperature control, in this new rat model, provides real-time evidence that glutamate levels in the interstitial space are enhanced during a low flow state of cerebral ischemia. Furthermore, not before demonstrated, glutamate transients are seen to occur during the first 90 s of reperfusion, and, to the best of our knowledge, the glutamate levels recorded by this technique are the highest in the literature. (C) 1998 Elsevier Science B.V. All rights reserved.