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

• Published in: Brain research 2001-03, Vol.895 (1), p.268-272
• Main Authors: Schurr, Avital, Payne, Ralphiel S, Miller, James J, Tseng, Michael T, Rigor, Benjamin M
• Format: Article
• Language: English
• Subjects: a-Cyano-4-hydroxycinnamate; Animals; Biological and medical sciences; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - physiology; Brain Ischemia - metabolism; Brain Ischemia - pathology; Brain Ischemia - physiopathology; Cardiac arrest; Carrier Proteins - drug effects; Carrier Proteins - metabolism; Cerebral ischemia; Coumaric Acids - pharmacology; Delayed neuronal damage; Energy metabolism; Energy Metabolism - drug effects; Energy Metabolism - physiology; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - pathology; Lactate transport; Lactic Acid - metabolism; Male; Medical sciences; Monocarboxylic Acid Transporters; Nerve Degeneration - metabolism; Nerve Degeneration - pathology; Nerve Degeneration - physiopathology; Neurology; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Rats; Rats, Sprague-Dawley; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(01)02082-0

Studies over the past decade have demonstrated that lactate is produced aerobically during brain activation and it has been suggested to be an obligatory aerobic energy substrate postischemia. It has been also hypothesized, based on in vitro studies, that lactate, produced by glia in large amounts during activation and/or ischemia/hypoxia, is transported via specific glial and neuronal monocarboxylate transporters into neurons for aerobic utilization. To test the role of lactate as an aerobic energy substrate postischemia in vivo, we employed the cardiac-arrest-induced transient global cerebral ischemia (TGI) rat model and the monocarboxylate transporter inhibitor α-cyano-4-hydroxycinnamate (4-CIN). Once 4-CIN was establish to cross the 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 delayed neuronal damage in the hippocampus than control, untreated rats, as measured 7 days post-TGI. We concluded that intra-ischemically-accumulated lactate is utilized aerobically as the main energy substrate immediately postischemia. Blockade of lactate transport into neurons prevents its utilization and, consequently, exacerbates delayed ischemic neuronal damage.