Intravenous phosphocreatine improves neurological outcome in focal cerebral ischaemia and reperfusion

Background: Intracellular phosphocreatine (PCr) acts as an anaerobe energy source to convert ADP to ATP and may thus be of potential benefit in ischaemic stroke. We investigated the effect of intravenous PCr on clinical outcome and infarct size in rats with transient focal cerebral ischaemia.

Methods: Male Wistar rats weighing 280 to 320 grams were subjected to 90 minutes of middle cerebral artery occlusion (MCA-O) by trans-carotid filament placement. During ischaemia, animals received normal saline (n=11) or PCr (n=12; 100mg/ml in normal saline) via the femoral vein. One ml was given as a bolus over 15 minutes followed by a continuous infusion of 1ml/h. Treatment with PCr started 30 minutes prior to MCA-O and ended 15 minutes after onset of reperfusion which was achieved by thread retraction. After 24 hours of reperfusion a blinded neurological score (Garcia score) was obtained. The rats were killed and infarct volumes were quantified using stained kryo-sections and a morphometric imaging system.

Results: Animals treated with PCr had a higher Garcia score reflecting better neurological outcome than controls (saline: 14,1±1,9; PCr: 16,0±1,0, p<0,01). Regarding infarct volume, there was a non-significant trend towards smaller infarcts in treated animals (saline: 70,8±54,2mm²; PCr: 50,0±4,2mm²).

Discussion: Our results show, that PCr improves neurological outcome in focal cerebral ischaemia. PCr may therefore be of potential benefit in acute stroke treatment.