Effects of Exogenous Excitatory Amino Acid Neurotransmitters on Blood–Brain Barrier Disruption in Focal Cerebral Ischemia

Abstract

This study was performed to determine whether exogenous N-methyl-D: -aspartate (NMDA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) would aggravate blood-brain barrier (BBB) disruption in focal cerebral ischemia in rats. Forty-five minutes after middle cerebral artery (MCA) occlusion, one of the following patches was applied to the exposed ischemic cerebral cortex of each rat: normal saline (control), 10(-5) M AMPA, 10(-4) M AMPA, 10(-5) M NMDA, or 10(-4) M NMDA. At 1 h after MCA occlusion, BBB permeability was determined by measuring the transfer coefficient (Ki) of (14)C-alpha-aminoisobutyric acid ((14)C-AIB). In all experimental groups, the Ki of the ischemic cortex (IC) was higher than that of the corresponding contralateral cortex (CC). The Ki of the IC of the animals treated with 10(-4) M AMPA or 10(-4) M NMDA was higher (+41%: P < 0.05 and +33%: P < 0.05, respectively) than that of the control animals. Our data demonstrated that exogenous NMDA or AMPA could further aggravate the BBB disruption in focal cerebral ischemia. Any insult increasing the release of excitatory neurotransmitters could further aggravate BBB disruption and brain edema during the ischemic period.