Focal ischemia enhances choline output and decreases acetylcholine output from rat cerebral cortex

Choline concentration is rate limiting in the synthesis of acetylcholine. There is a negative arteriovenous difference for choline concentration across the brain, indicating the steady output of choline from this organ. Cerebral ischemia may increase extracellular choline concentration by interfering with its removal by the circulation and by enhancing its net production from phospholipids. We tested this hypothesis in six rats subjected to middle cerebral artery occlusion. We determined choline and acetylcholine output from the ischemic cerebral cortex by analyzing their concentrations in the fluid contained in cortical cups by gas chromatography-mass spectrometry. Mean +/- SEM choline output over 40 minutes before ischemia (baseline value) was 31.1 +/- 1.6 pmol/min/cm2. During ischemia, mean +/- SEM choline output rose to 100.8 +/- 13, 97.3 +/- 12.7, 100 +/- 22.4, and 93.1 +/- 16.9 pmol/min/cm2 in four consecutive 10-minute periods, respectively. Mean +/- SEM acetylcholine output was 15.6 +/- 1.1 before and 5.9 +/- 1.2, 8.3 +/- 2.6, 8.6 +/- 2.1, and 13.7 +/- 4.6 pmol/min/cm2 in the four 10-minute collection periods during ischemia. All four choline values and the first acetylcholine value during ischemia were significantly different from their respective baseline values. We conclude that ischemia induces an increase in extracellular choline concentration with possible implications for acetylcholine metabolism. The attending transient decline in acetylcholine output may be due to impaired release due to local hypoxia or to decreased acetylcholine synthesis.