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

• Published in: The American journal of surgery 2013-12, Vol.206 (6), p.840-846
• Main Authors: Pascual, Jose L., M.D., Ph.D, Murcy, Mohammad A., M.D, Li, Shenghui, M.D, Gong, Wanfeng, M.D, Eisenstadt, Rachel, B.A, Kumasaka, Kenichiro, M.D, Sims, Carrie, M.D., M.S, Smith, Douglas H., M.D, Browne, Kevin, B.A, Allen, Steve, M.D, Baren, Jill, M.D
• Format: Article
• Language: English
• Subjects: Animals; Blood; Blood-brain barrier; Blood-Brain Barrier - drug effects; Brain damage; Brain Edema - etiology; Brain Edema - metabolism; Brain Edema - prevention & control; Brain Injuries - complications; Brain Injuries - drug therapy; Brain Injuries - metabolism; Capillary Permeability - drug effects; Cerebrovascular Circulation - drug effects; Cytotoxicity; Disease Models, Animal; Endothelium; Free radicals; Head injuries; Intravital microscopy; Male; Mice; Microscopy; Neutrophil; Neutrophil Activation - drug effects; Permeability; Progesterone; Progesterone - pharmacokinetics; Progestins - pharmacokinetics; Rodents; Surgery; Traumatic brain injury
• ISSN: 0002-9610; 1879-1883
• DOI: 10.1016/j.amjsurg.2013.07.016

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.