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

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posted on 2015-02-05, 12:40 authored by R. Wong, Claire L. Gibson, D. A. Kendall, P. M. Bath
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.

Funding

This work was supported by the Medical Research Council (grant number G0800129). Dr Claire Gibson was granted a period of study leave from the University of Leicester, which contributed to the completion to this work.

History

Citation

Wong et al.: Evaluating the translational potential of progesterone treatment following transient cerebral ischaemia in male mice. BMC Neuroscience 2014 15:131.

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/Themes/Neuroscience & Behaviour

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  • VoR (Version of Record)

Published in

Wong et al.: Evaluating the translational potential of progesterone treatment following transient cerebral ischaemia in male mice. BMC Neuroscience 2014 15:131.

Publisher

BioMed Central, United Kingdom

issn

1471-2202

eissn

1471-2202

Copyright date

2014

Available date

2015-02-05

Publisher version

http://www.biomedcentral.com/1471-2202/15/131

Notes

PMCID: PMC4255926

Language

en

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