• Jose L Pascual, Mohammad A Murcy, Shenghui Li, Wanfeng Gong, Rachel Eisenstadt, Kenichiro Kumasaka, Carrie Sims, Douglas H Smith, Kevin Browne, Steve Allen, and Jill Baren.
• 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.
• Am. J. Surg. 2013 Dec 1; 206 (6): 840-5; discussion 845-6.

BackgroundProgesterone (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).MethodsCD1 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.ResultsCompared 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).ConclusionsPRO reduces live pericontusional EC/PMN and BBB macromolecular leakage after TBI. Direct PRO effects on the microcirculation warrant further investigation.Copyright © 2013 Elsevier Inc. All rights reserved.

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