The pre-ischaemic neuroprotective effects of the polyamine analogues BU43b and BU36b in permanent and transient focal cerebral ischaemia models in mice.
The present study investigated the neuroprotective potential of two novel polyamine analogues, BU43b and BU36b, when administered 30 min prior to cerebral ischaemia. Neuroprotection in a permanent and a transient focal cerebral ischaemia mouse model (induced by intraluminal middle cerebral artery occlusion (MCAO)) was investigated using a range of histological and behavioural assessments. In the permanent ischaemia model, BU43b reduced oedema and showed a trend towards reduction in %HLV (percentage hemisphere lesion volume) when administered at a dose of 30 mg/kg i.p. Following transient ischaemia, treatment with BU43b decreased the %HLV and reduced oedema when administered at 30 mg/kg. BU43b also improved the locomotor activity (LMA) in MCAO mice at both 20 mg/kg and 30 mg/kg doses. BU36b was less effective than BU43b in both the permanent and the transient models, with its most pronounced effect being a trend towards reduction in oedema in both models. These results demonstrate that BU43b administered 30 min before ischaemia provided a good level of neuroprotection in the two models of cerebral ischaemia used and may have potential as a neuroprotective treatment for stroke.
Department of Pharmacology, School of Pharmacy, Trinity College Dublin, Ireland. junli@uchc.edu
Jun
J
Li
Martin C
MC
Henman
Jeffrey
J
Atkinson
Solomon
S
Fixon-Owoo
Turgut
T
Tatlisumak
Graham G
GG
Shaw
Karen M
KM
Doyle
D000818:Animals; D001522:Behavior, Animal; D001929:Brain Edema / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D002546:Ischemic Attack, Transient / Q000150:complications / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000737:chemistry; D011073:Polyamines / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D045442:Rotarod Performance Test / Q000379:methods; D013778:Tetrazolium Salts; D013997:Time Factors
C511984:BU36b polyamine; C511983:BU43b polyamine; D018696:Neuroprotective Agents; D011073:Polyamines; D013778:Tetrazolium Salts; C009591:triphenyltetrazolium