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

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 mu m/min P < .001), total EC/PMN adhesion (2.0 +/- .4 vs .8 +/- .1 PMN/100 mu m, 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. (C) 2013 Elsevier Inc. All rights reserved.