CITICOLINE FOR TREATMENT OF EXPERIMENTAL FOCAL ISCHEMIA - HISTOLOGIC AND BEHAVIORAL OUTCOME

We evaluated the effect of chronic administration of CDP-choline, an i ntermediate of phospholipid synthesis, on outcome from middle cerebral artery occlusion, ranging from 30 to 120 min in duration, in spontane ously hypertensive rats. Rats were randomly assigned to either CDP-cho line 500 mg kg(-1) or saline. CDP-choline treatment was initiated by i ntraperitoneal injection 15 min after the onset of ischemia and contin ued once a day for 14 days. Morphologic damage and behavioral dysfunct ion (motor and sensorimotor performance) were evaluated, and the maxim al morphologic damage (Vol(max)), maximal behavioral dysfunction (BDma x) as well as the duration of ischemia producing half-maximal morpholo gic damage (T-50) or behavioral dysfunction (BD50) were calculated usi ng a curve-fitting program (ALLFIT). Ischemia in control animals produ ced a Vol(max) of 103.3+/-13.6 mm(3). CDP-choline did not affect this value (Vol(max) of 101.6+/-11.4 mm(3)). However, CDP-choline significa ntly extended the T-50 from 38.3+/-5.9 to 60.5+/-4.3 min (p < 0.05). S imilar to the morphologic outcome, CDP-choline had no effect on BDmax but significantly extended BD50 from 41.9+/-4.6 to 72.9+/-24.5 min (p < 0.05). Our results suggest that the effectiveness of CDP-choline is greater in animals demonstrating submaximal ischemic injury which in t his model is produced by 30-75 min of ischemia (effect on T-50 and BD5 0), than in animals suffering maximal ischemic injury produced by isch emia longer than 75 min (no effect on Vol(max) and BDmax). These resul ts may reflect a threshold of biological membrane damage within which CDP-choline is able to restore phospholipid content/arrangement and re tain membrane integrity.