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.
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:CD1mice 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.
Authors: Adel Helmy; Maria-Grazia De Simoni; Mathew R Guilfoyle; Keri L H Carpenter; Peter J Hutchinson Journal: Prog Neurobiol Date: 2011-09-16 Impact factor: 11.685
Authors: Joshua A Marks; Shenghui Li; Wanfeng Gong; Paymon Sanati; Rachel Eisenstadt; Carrie Sims; Douglas H Smith; Patrick M Reilly; Jose L Pascual Journal: J Trauma Acute Care Surg Date: 2012-08 Impact factor: 3.313
Authors: Katsuhiro Nagata; Kenichiro Kumasaka; Kevin D Browne; Shengjie Li; Jesse St-Pierre; John Cognetti; Joshua Marks; Victoria E Johnson; Douglas H Smith; Jose L Pascual Journal: J Trauma Acute Care Surg Date: 2016-12 Impact factor: 3.313
Authors: Shengjie Li; Joshua A Marks; Rachel Eisenstadt; Kenichiro Kumasaka; Davoud Samadi; Victoria E Johnson; Daniel N Holena; Steven R Allen; Kevin D Browne; Douglas H Smith; Jose L Pascual Journal: J Trauma Acute Care Surg Date: 2015-07 Impact factor: 3.313
Authors: Shengjie Li; Rachel Eisenstadt; Kenichiro Kumasaka; Victoria E Johnson; Joshua Marks; Katsuhiro Nagata; Kevin D Browne; Douglas H Smith; Jose L Pascual Journal: J Trauma Acute Care Surg Date: 2016-03 Impact factor: 3.313
Authors: Kenichiro Kumasaka; Joshua A Marks; Rachel Eisenstadt; Mohammad A Murcy; Davoud Samadi; Shengjie Li; Victoria Johnson; Kevin D Browne; Douglas H Smith; C William Schwab; Jose L Pascual Journal: Am J Surg Date: 2014-09-22 Impact factor: 2.565
Authors: Lesley D O'Brien; Terry L Smith; Giulia Donvito; Benjamin F Cravatt; Jason Newton; Sarah Spiegel; Thomas M Reeves; Linda L Phillips; Aron H Lichtman Journal: Cannabis Cannabinoid Res Date: 2021-06-17