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

Jose L. Pascual, Mohammad A. Murcy, Shenghui Li, Wanfeng Gong, Rachel Eisenstadt, Kenichiro Kumasaka, Carrie Sims, Douglas H. Smith, Kevin Browne, Steve Allen, Jill Baren

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)840-846
Number of pages7
JournalAmerican Journal of Surgery
Volume206
Issue number6
DOIs
StatePublished - Dec 2013

All Science Journal Classification (ASJC) codes

  • Surgery

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