REAL-TIME MEASUREMENT OF ISCHEMIA-EVOKED GLUTAMATE RELEASE IN THE CEREBRAL-CORTEX OF 4 AND 11 VESSEL RAT OCCLUSION MODELS

Interstitial levels of the neurotransmitter glutamate and cerebral blo od flow changes were compared in two models of rat forebrain ischemia using the dialysis electrode technique and laser doppler flowmetry wit h brain temperature controlled. Ten-minute periods of cerebral ischemi a were elicited by the four and an eleven vessel occlusion and compare d to carotid artery transection. Elapsed time from the onset of ischem ia 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, Concomit antly, cerebral glutamate levels rose to 255.7 +/- 72.8 mu mol l(-1) i n 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. D uring 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 anim als. Following reperfusion, glutamate levels in the 4VO and 11VO anima ls returned towards basal levels.This study demonstrates that 11VO cau ses 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, re sults in a higher interstitial level of glutamate than a 'no flow' sta te, as exhibited by the 11VO technique. The dialysis electrode, used s imultaneously with laser doppler flowmetry, real-time data acquisition , and continuous brain temperature control, in this new rat model, pro vides real-time evidence that glutamate levels in the interstitial spa ce are enhanced during a low flow state of cerebral ischemia. Furtherm ore, not before demonstrated, glutamate transients are seen to occur d uring the first 90 s of reperfusion, and, to the best of our knowledge , the glutamate levels recorded by this technique are the highest in t he literature. (C) 1998 Elsevier Science B.V. All rights reserved.