The pre-ischaemic neuroprotective effects of N¹-dansyl-spermine in a transient focal cerebral ischaemia model in mice

The pre-ischaemic neuroprotective potential of a novel polyamine/NMDA antagonist N¹-dansyl-spermine (1-5 mg kg^-1) was studied in a transient focal cerebral ischaemia model in mice in comparison to a reference compound, MK-801 (1 or 3 mg kg^-1). The intraluminal suture transient middle cerebral artery occlusion (MCAO) model was used. N¹-dansyl- spermine and MK-801 were administered (i.p.) 30 min prior to ischaemia. A range of histological and behavioural assessments was employed. N¹-dansyl- spermine had a comparable effect to MK-801 at reducing the percentage hemisphere lesion volume (%HLV) at the doses tested. Furthermore, N¹-dansyl- spermine reduced the ischaemic brain oedema, which MK-801 did not. N ¹-dansyl-spermine significantly reversed the decrease of locomotor activity (LMA) caused by the MCAO and showed a significant effect at improving the rotarod performance impaired by MCAO. In contrast, MK-801 had no beneficial effect on sensorimotor function and even worsened the LMA. These results clearly demonstrate the pre-ischaemic neuroprotective effect of N¹-dansyl- spermine in a transient focal cerebral ischaemia model.