title: Evaluating the translational potential of progesterone treatment following transient cerebral ischaemia in male mice.
abstract: BACKGROUND
  Progesterone is neuroprotective in numerous preclinical CNS injury models including cerebral ischaemia. The aim of this study was two-fold; firstly, we aimed to determine whether progesterone delivery via osmotic mini-pump would confer neuroprotective effects and whether such neuroprotection could be produced in co-morbid animals.
  
  
  RESULTS
  Animals underwent transient middle cerebral artery occlusion. At the onset of reperfusion, mice were injected intraperitoneally with progesterone (8 mg/kg in dimethylsulfoxide). Adult and aged C57 Bl/6 mice were dosed additionally with subcutaneous infusion (1.0 μl/h of a 50 mg/ml progesterone solution) via implanted osmotic minipumps. Mice were allowed to survive for up to 7 days post-ischaemia and assessed for general well-being (mass loss and survival), neurological score, foot fault and t-maze performance. Progesterone reduced neurological deficit [F(1,2) = 5.38, P = 0.027] and number of contralateral foot-faults [F(1,2) = 7.36, P = 0.0108] in adult, but not aged animals, following ischaemia. In hypertensive animals, progesterone treatment lowered neurological deficit [F(1,6) = 18.31, P = 0.0001], reduced contralateral/ipsilateral alternation ratio % [F(1,2) = 17.05, P = 0.0006] and time taken to complete trials [F(1,2) = 15.92, P = 0.0009] for t-maze.
  
  
  CONCLUSIONS
  Post-ischemic progesterone administration via mini-pump delivery is effective in conferring functional improvement in a transient MCAO model in adult mice. Preliminary data suggests such a treatment regimen was not effective in producing a protective effect in aged mice. However, in hypertensive mice, who received post-ischemic progesterone intraperitoneally at the onset of reperfusion had better functional outcomes than control hypertensive mice.
authors.forename: Raymond
authors.initials: R
authors.lastname: Wong
authors.affiliation: School of Psychology, University of Leicester, Henry Wellcome Building, Leicester LE1 9HN, UK. cg95@le.ac.uk.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Gibson
authors.forename: David A
authors.initials: DA
authors.lastname: Kendall
authors.forename: Philip M W
authors.initials: PM
authors.lastname: Bath
mesh_terms: D000367:Age Factors; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D004353:Drug Evaluation, Preclinical; D006973:Hypertension / Q000503:physiopathology; D020244:Infarction, Middle Cerebral Artery; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D011374:Progesterone / Q000008:administration & dosage*; D011897:Random Allocation; D020127:Recovery of Function / Q000187:drug effects; D012720:Severity of Illness Index; D016019:Survival Analysis
chemical_list: D018696:Neuroprotective Agents; D011374:Progesterone