Effects of metabotropic glutamate receptor stimulation on cerebral O2 consumption and blood flow during focal cerebral ischemia in rats.

Abstract

This investigation was performed to evaluate the effects of ACPD [(1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid], a metabotropic glutamate receptor agonist, on cerebral O2 consumption during focal cerebral ischemia. Male Wistar rats were placed in control (n = 7) and ACPD (n = 7) groups under isoflurane anesthesia. Twenty minutes after middle cerebral artery (MCA) occlusion, gauze sponges with 10(-5) M ACPD or normal saline were placed on the ischemic cortex (IC) for a period of 40 min and were changed every 10 min. One hour after MCA occlusion, regional cerebral blood flow (rCBF) was determined using the C14-iodoantipyrine autoradiographic technique. Regional arterial and venous oxygen saturation were determined using microspectrophotometry. There were no statistical differences in vital signs, blood gases, and hemoglobin between the groups. In the control group, the cerebral blood flow and oxygen consumption of the IC were significantly lower than the contralateral cortex (rCBF: 45 +/- 11 vs. 110 +/- 11 ml/min/100 g, O2 consumption: 2.9 +/- 0.4 vs. 5.4 +/- 1.1 ml O2/min/100 g). ACPD did not change regional cerebral blood flow of the IC, but did significantly increase the oxygen extraction (7.8 +/- 0.2 vs. 6.9 +/- 0.3 ml O2/100 ml) and oxygen consumption of the IC (4.3 +/- 1.5 vs. 2.9 +/- 0.4) compared to the control IC. Our data demonstrated that topical application of 10(-5) M ACPD to the ischemic area worsened cerebral O2 balance. These data suggest that metabotropic glutamate receptors are not maximally activated during ischemia in the temporal cortex.