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Am J Surg. 2013 Dec;206(6):840-5; discussion 845-6. doi: 10.1016/j.amjsurg.2013.07.016. Epub 2013 Oct 7.

Neuroprotective effects of progesterone in traumatic brain injury: blunted in vivo neutrophil activation at the blood-brain barrier.

Author information

1
Department of Surgery, Division of Traumatology, Surgical Critical Care and Emergency Surgery, Perelman School of Medicine at the University of Pennsylvania, The Trauma Center at Penn, 3400 Spruce Street, Maloney Building, 5th Floor, Philadelphia, PA 19104, USA. Electronic address: jose.pascual@uphs.upenn.edu.

Abstract

BACKGROUND:

Progesterone (PRO) may confer a survival advantage in traumatic brain injury (TBI) by reducing cerebral edema. We hypothesized that PRO reduces edema by blocking polymorphonuclear (PMN) interactions with endothelium (EC) in the blood-brain barrier (BBB).

METHODS:

CD1 mice received repeated PRO (16 mg/kg intraperitoneally) or vehicle (cyclodextrin) for 36 hours after TBI. Sham animals underwent craniotomy without TBI. The modified Neurological Severity Score graded neurologic recovery. A second craniotomy allowed in vivo observation of pial EC/PMN interactions and vascular macromolecule leakage. Wet/dry ratios assessed cerebral edema.

RESULTS:

Compared with the vehicle, PRO reduced subjective cerebral swelling (2.9 ± .1 vs 1.2 ± .1, P < .001), PMN rolling (95 ± 1.8 vs 57 ± 2.0 cells/100 μm/min, P < .001), total EC/PMN adhesion (2.0 ± .4 vs .8 ± .1 PMN/100 μm, P < .01), and vascular permeability (51.8% ± 4.9% vs 27.1% ± 4.6%, P < .01). TBI groups had similar a Neurological Severity Score and cerebral wet/dry ratios (P > .05).

CONCLUSIONS:

PRO reduces live pericontusional EC/PMN and BBB macromolecular leakage after TBI. Direct PRO effects on the microcirculation warrant further investigation.

KEYWORDS:

Blood-brain barrier; Endothelium; Intravital microscopy; Neutrophil; Progesterone; Traumatic brain injury

PMID:
24112683
PMCID:
PMC4149185
DOI:
10.1016/j.amjsurg.2013.07.016
[Indexed for MEDLINE]
Free PMC Article

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