Polyamines in the brain: distribution, biological interactions, and their potential therapeutic role in brain ischaemia

The endogenous polyamines (spermine, spermidine, and putrescine) are present at relatively high concentrations in the mammalian brain and play crucial roles in a variety of aspects of cell functioning. Stroke is the third most common cause of death and the leading cause of disability among adults in the western world. Brain polyamine levels change dramatically following cerebral ischaemia. Polyamines may be involved in the pathophysiological processes underlying brain ischaemia through several possible mechanisms. These include direct effects on ion channels and receptors modulating potassium, and most importantly calcium trafficking, or through the production of toxic metabolites. Considerable evidence shows that the noncompetitive polyamine antagonists, ifenprodil and eliprodil, are neuroprotective. Interestingly, novel polyamine analogues, such as N1-dansylspermine, BU36b, and BU43b, have also recently been shown to have neuroprotective potential. The exact mechanisms of the neuroprotection afforded by the polyamine antagonists and their clinical applicability is worthy of further study.Dr. Tatlisumak was supported by the Helsinki University Central Hospital, the University of Helsinki, the Finnish Academy of Sciences, and the Sigrid Juselius Foundation. The authors express their most sincere respects and gratitude to late Professor GG Shaw of Trinity College, Ireland, a great teacher and scientist who left us at his most productive age