TY - JOUR
T1 - Neuroprotective effects of progesterone in traumatic brain injury
T2 - Blunted in vivo neutrophil activation at the blood-brain barrier
AU - Pascual, Jose L.
AU - Murcy, Mohammad A.
AU - Li, Shenghui
AU - Gong, Wanfeng
AU - Eisenstadt, Rachel
AU - Kumasaka, Kenichiro
AU - Sims, Carrie
AU - Smith, Douglas H.
AU - Browne, Kevin
AU - Allen, Steve
AU - Baren, Jill
PY - 2013/12
Y1 - 2013/12
N2 - 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.
AB - 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.
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U2 - 10.1016/j.amjsurg.2013.07.016
DO - 10.1016/j.amjsurg.2013.07.016
M3 - Article
C2 - 24112683
AN - SCOPUS:84889068233
SN - 0002-9610
VL - 206
SP - 840
EP - 846
JO - American Journal of Surgery
JF - American Journal of Surgery
IS - 6
ER -