Evaluating the translational potential of progesterone treatment following transient cerebral ischaemia in male mice

BMC Neuroscience

Philip MW Bath¹  David A Kendall²  Claire L Gibson³  Raymond Wong¹ 

[1]Division of Stroke, University of Nottingham, Clinical Sciences Building, City Hospital Campus, Hucknall Road, Nottingham NG5 1 PB, UK

[2]School of Biomedical Sciences, University of Nottingham, Medical School, Queen’s Medical Centre, Nottingham NG7 2UH, UK

[3]School of Psychology, University of Leicester, Henry Wellcome Building, Leicester LE1 9HN, UK

关键词: Mouse;    Functional;    Co-morbid;    Mini-pump;    Stroke;    Progesterone;   

Others  :  1090438
DOI  :  10.1186/s12868-014-0131-5

 received in 2014-08-18, accepted in 2014-11-20,  发布年份 2014

【 摘 要 】

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.

Conclusion

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.

【 授权许可】

   
2014 Wong et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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