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.