Ischemia-Induced Release of Amino Acids in the Hippocampus of Aged Hypertensive Rats

Abstract

We have recently demonstrated the age-related vulnerability of hippocampal neurons to 20-min forebrain ischemia in spontaneously hypertensive rats (SHR). In the present study, we investigated the effect of aging on the release of amino acids in the hippocampus during transient cerebral ischemia for 20 min. Concentrations of extracellular amino acids and cerebral blood flow in the CA1 subfield were examined by an in vivo brain dialysis technique and a hydrogen clearance method, respectively, in adult (5–7 month) and aged (19–23 month) female SHR. During cerebral ischemia by bilateral carotid artery occlusion, cerebral blood flow to the hippocampus decreased to 20% of the resting values in both groups. After recirculation, both groups showed delayed hypoperfusion which was more prominent in the aged SHR. In the adult rats, concentrations of both aspartate and glutamate increased to ∼8-fold of the resting values during ischemia. The elevation of these excitatory amino acids in the adult SHR was not significantly different from that in the aged rats. In contrast, the concentration of taurine increased 26-fold in the adult SHR but only 16-fold in the aged rats. Changes in other amimo acids were not different between the two groups. These results indicate that an imbalance of excitatory and inhibitory amino acids, e.g., smaller release of taurine, during ischemia may, at least in part, contribute to the age-related vulnerability of hippocampal neurons to transient cerebral ischemia in SHR.