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. N1-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.
Li
Jun
J
Department of Pharmacology, School of Pharmacy, Trinity College Dublin, Ireland. junli@uchc.edu
Henman
Martin C
MC
Tatlisumak
Turgut
T
Shaw
Graham G
GG
Doyle
Karen M
KM
D000818:Animals; D001921:Brain / Q000473:pathology; D001929:Brain Edema / Q000473:pathology / Q000517:prevention & control; D003619:Dansyl Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D045442:Rotarod Performance Test / Q000379:methods; D013096:Spermine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013778:Tetrazolium Salts; D013997:Time Factors
D003619:Dansyl Compounds; C105932:N(1)-dansylspermine; D018696:Neuroprotective Agents; D013778:Tetrazolium Salts; D013096:Spermine; D016291:Dizocilpine Maleate; C009591:triphenyltetrazolium