Blockade of lactate transport exacerbates delayed neuronal damage in a ratmodel of cerebral ischemia

Studies over the past decade have demonstrated that lactate is produced aer obically during brain activation and it has been suggested to be an obligat ory aerobic energy substrate postischemia. It has been also hypothesized, b ased on in vitro studies, that lactate, produced by glia in large amounts d uring activation and/or ischemia/hypoxia. is transported via specific glial and neuronal monocarboxylate transporters into neurons For aerobic utiliza tion. To test the role of lactate as an aerobic energy substrate postischem ia in vivo, we employed the cardiac-arrest-induced transient global cerebra l ischemia (TGI) rat model and the monocarboxylate transporter inhibitor al pha -cyano-4-hydroxycinnamate (4-CIN). Once 4-CIN was establish to cross th e blood-brain barrier. rats were treated with the inhibitor 60 min prior to a 5-min TGI. These rats exhibited a significantly greater degree of delaye d neuronal damage in the hippocampus than control, untreated rats, as measu red 7 days post-TGI. We concluded that intra-ischemically-accumulated lacta te is utilized aerobically as the main energy substrate immediately postisc hemia. Blockade of lactate transport into neurons prevents its utilization and, consequently, exacerbates delayed ischemic neuronal damage. (C) 2001 E lsevier Science B.V. All rights reserved.