An investigation of the role of the polyamines in epilepsy and cerebral ischaemia

Abstract

The polyamines, spermine and spermidine, are ubiquitous in nature but are found in especially high concentrations in brain tissue. The polyamines are required for cell growth and differentiation but in high doses are neurotoxic. A dose of 100μg spermine given by the intracerebroventricular route results in the development of CNS excitation, culminating in tonic convulsion, within 8 hours of injection. The work presented here aimed to further characterise this CNS excitation. It was previously shown that both the NMDA receptor and calcium channels may be involved in this syndrome. Therefore, NMDA receptor antagonists, calcium channel antagonists and a novel polyamine analogue were utilised to investigate the spermine induced CNS excitation. Spermine is known to enhance the activity of the NMDA receptor through an action on an extracellular binding site on the NMDA receptor macrocomplex. An in vivo model was used to investigate this spermine enhancement of NMDA activity. In an attempt to characterise the action of spermine on the NMDA receptor, a calcium channel antagonist, polyamine antagonists and a novel polyamine analogue, N1- dansylspermine, were used.