Effect of propentofylline (HWA 285) on extracellular purines and excitatory amino acids in CA1 of rat hippocampus during transient ischaemia

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Abstract
1 The adenosine uptake blocker propentofylline (HWA 285) has previously been shown to protect hippocampal CA1 pyramidal cells from ischaemia-induced delayed neuronal death. The influence of propentofylline, on the extracellular concentrations of purines, aspartate and glutamate in the CA1 of the rat hippocampus during transient forebrain ischaemia was investigated. 2 Twenty min of ischaemia was induced by four-vessel occlusion in Wistar rats, extracellular compounds were sampled by use of microdialysis and EEG was recorded by a tungsten electrode attached to the dialysis probe. 3 Propentofylline (10 mgkg−1 i.p.) did not influence the basal levels of any of the compounds in the hippocampal dialysates. 4 The EEG became isoelectric within 20 s after induction of ischaemia. 5 Extracellular adenosine, inosine, hypoxanthine, aspartate and glutamate increased several fold during ischaemia and remained elevated during early reflow. Within 2 h of reperfusion the concentration of all compounds was normalized. Xanthine increased upon reperfusion and remained elevated after 2 h. 6 Propentofylline (10 mg kg−1 i.p.) administered 15 min before ischaemia significantly enhanced the ischaemia-evoked increase of adenosine but attenuated the increases of the other purine catabolites and of glutamate. 7 In separate in vitro experiments, propentofylline did not inhibit adenosine deaminase activity. 8 The present data show that propentofylline enhances extracellular adenosine and lowers extracellular glutamate in vivo during ischaemia. These findings may be important in relation to the neuroprotective properties of propentofylline.