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

被引:42
作者
Pascual, Jose L. [1 ]
Murcy, Mohammad A. [1 ]
Li, Shenghui [2 ]
Gong, Wanfeng [1 ]
Eisenstadt, Rachel [1 ]
Kumasaka, Kenichiro [1 ]
Sims, Carrie [1 ]
Smith, Douglas H. [3 ]
Browne, Kevin [3 ]
Allen, Steve [1 ]
Baren, Jill [4 ]
机构
[1] Univ Penn, Div Traumatol Surg Crit Care & Emergency Surg, Dept Surg, Perelman Sch Med,Trauma Ctr Penn, Philadelphia, PA 19104 USA
[2] Tianjin Med Univ, Tianjin Neurol Inst, Dept Neurosurg, Tianjin, Peoples R China
[3] Univ Penn, Dept Neurosurg, Ctr Brain Injury & Repair, Perelman Sch Med, Philadelphia, PA 19104 USA
[4] Univ Penn, Dept Emergency Med, Perelman Sch Med, Philadelphia, PA 19104 USA
关键词
Intravital microscopy; Neutrophil; Endothelium; Blood-brain barrier; Traumatic brain injury; Progesterone; HYPERTONIC SALINE; INFLAMMATION; HORMONES; SODIUM; EDEMA;
D O I
10.1016/j.amjsurg.2013.07.016
中图分类号
R61 [外科手术学];
学科分类号
摘要
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.
引用
收藏
页码:840 / 845
页数:6
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