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The neuroprotective effect of progesterone after traumatic brain injury in male mice is independent of both the inflammatory response and growth factor expression

Authors

  • Nigel C. Jones,

    1. Institute of Cell Signalling, University of Nottingham, Clifton Blvd., Nottingham NG7 2UH, UK
    2. Institute of Neuroscience, University of Nottingham, Nottingham NG7 2UH, UK
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  • Despina Constantin,

    1. Institute of Cell Signalling, University of Nottingham, Clifton Blvd., Nottingham NG7 2UH, UK
    2. Institute of Neuroscience, University of Nottingham, Nottingham NG7 2UH, UK
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  • Malcolm J. W. Prior,

    1. Institute of Neuroscience, University of Nottingham, Nottingham NG7 2UH, UK
    2. Sir Peter Mansfield Magnetic Resonance Centre, University of Nottingham, Nottingham NG7 2UH, UK
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  • Peter G. Morris,

    1. Institute of Neuroscience, University of Nottingham, Nottingham NG7 2UH, UK
    2. Sir Peter Mansfield Magnetic Resonance Centre, University of Nottingham, Nottingham NG7 2UH, UK
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  • Charles A. Marsden,

    1. Institute of Neuroscience, University of Nottingham, Nottingham NG7 2UH, UK
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  • Sean Murphy

    1. Institute of Cell Signalling, University of Nottingham, Clifton Blvd., Nottingham NG7 2UH, UK
    2. Institute of Neuroscience, University of Nottingham, Nottingham NG7 2UH, UK
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Dr Sean Murphy, 1Institute of Cell Signalling, as above.
E-mail: sean.murphy@nottingham.ac.uk

Abstract

Previous studies suggest that progesterone may possess neuroprotective properties after traumatic insult but, with the exception of reduced formation of cerebral oedema, limited experimental evidence has been presented to support this claim. In the present study we focused on the effect of progesterone treatment on structural and functional deficits in an experimental model of traumatic brain injury. Female mice exhibited significantly (P = 0.0445) reduced lesion volumes compared with males after aseptic cryogenic cerebral injury (ACI), suggesting that female sex steroids provide protection against this injury. In male mice, progesterone treatment after injury (three intraperitoneal doses of 8 mg/kg) reduced lesion volume (P = 0.0429) and improved performance in a spatial cognitive task (Morris water maze; P = 0.0014). However, progesterone had no demonstrable effect on the formation of oedema as measured using T2-weighted magnetic resonance imaging, nor did it affect brain water content. The pro-inflammatory cytokines TNF-α and IL-1β, and growth factors BDNF and G-CSF, were all strongly transcriptionally activated after ACI. However, progesterone administration did not affect expression of these genes. This study provides strong evidence that progesterone possesses neuroprotective properties in a mouse model of traumatic brain injury, but suggests that the steroid achieves this effect through mechanism(s) independent of the inflammatory response or growth factor up-regulation.

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