Polyamines and polyamine antagonists in cerebral ischaemia

Abstract

Polyamines are ubiquitous components of all eukaryotic cells and are found in brain tissue. A number of studies have shown that changes in the levels of polyamines occur following cerebral ischaemia. However, whether polyamines are neurotoxic or neuroprotective in ischaemia still remains unclear, although most of the evidence points to a toxic effect. The polyamine/NMDA antagonist N1-dansyl-spermine has been shown to be neuroprotective in a global ischaemia model. However, at the onset of the present study, the neuroprotective potential of this compound was not known in using focal ischaemia models, which are of more clinical relevance. Very recently, more novel polyamine analogues (BU31b, BU37b, BU33b, BU36b and BU43b) have been synthesized. These compounds, with the exception of BU37b, have shown some polyamine antagonist potential in vivo. Therefore these polyamine analogues are candidate neuroprotective agents. The pre-ischaemic effect of all these compounds mentioned above was investigated in the present study. This investigation also aimed to shed light on the role of the polyamines in ischaemia.