title: Effect of amplitude and duration of impulsive pressure on endothelial permeability in in vitro fluid percussion trauma.
abstract: BACKGROUND
  Intracranial pressure changes during head impact cause brain injuries such as vasogenic edema and cerebral contusion. However, the influence of impulsive pressure on endothelial function has not yet been fully studied in vitro. In this study, we developed a pressure loading device that produced positive and negative pressures by modifying an in vitro fluid percussion model and examined the effects of the amplitude and duration of the pressures on endothelial permeability.
  
  
  METHODS
  Human umbilical vein endothelial cells were subjected to three types of positive pressure (average amplitude/average duration of 352 kPa/23 ms, 73 kPa/27 ms, and 70 kPa/44 ms) and three types of negative pressure (-72 kPa/41 ms, -67 kPa/104 ms, and -91 kPa/108 ms), and the transendothelial electrical resistance (TEER) was measured between 15 min and 24 h after pressure loading for quantifying the formation of an integral monolayer of endothelial cells. After loading, vascular endothelial- (VE-) cadherin, an endothelium-specific cell-cell adhesion molecule involved in endothelial barrier function, was stained and observed using fluorescence microscopy.
  
  
  RESULTS
  The pressure loading device could produce positive pressure pulses with amplitudes of 53-1348 kPa and durations of 9-29.1 ms and negative pressure pulses with amplitudes of -52 - -93 kPa and durations of 42.9-179.5 ms. The impulsive pressure reduced the TEER associated with the change in VE-cadherin localization. Additionally, TEER decreased considerably at 15 min and 6 h post-loading, with these changes being significant in positive pressure with larger amplitude and shorter duration and in all types of negative pressures compared to pre-loading.
  
  
  CONCLUSIONS
  The changes in intracranial pressure during head impact impair endothelial barrier function by the disruption of the integrity of endothelial cell-cell junctions, and the degree of increase in endothelial permeability depends on the amplitude, duration, and direction (compressive and tensile) of the impulsive pressure.
authors.affiliation: Graduate School of System Design, Tokyo Metropolitan University, Tokyo, Japan. nakadate@tmu.ac.jp.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Nakadate
authors.forename: Koji
authors.initials: K
authors.lastname: Inuzuka
authors.forename: Suguru
authors.initials: S
authors.lastname: Akanuma
authors.forename: Akira
authors.initials: A
authors.lastname: Kakuta
authors.forename: Shigeru
authors.initials: S
authors.lastname: Aomura
mesh_terms: D001930:Brain Injuries / Q000473:pathology* / Q000503:physiopathology; D015820:Cadherins / Q000378:metabolism; D002196:Capillaries / Q000378:metabolism; D017097:Electric Impedance; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D057446:Hydrodynamics; D008422:Materials Testing / Q000295:instrumentation*; D010539:Permeability; D011312:Pressure; D021381:Protein Transport
chemical_list: D015820:Cadherins
references.citation: Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9815-20
references.pmid: 10449777
references.citation: Am J Physiol Lung Cell Mol Physiol. 2003 Oct;285(4):L785-97
references.pmid: 12639843
references.citation: J Surg Res. 1991 Nov;51(5):417-24
references.pmid: 1758175
references.citation: Annu Rev Biomed Eng. 2011 Aug 15;13:91-126
references.pmid: 21529164
references.citation: J Trauma. 1996 Jul;41(1):129-35
references.pmid: 8676405
references.citation: Neurobiol Dis. 2004 Oct;17(1):29-43
references.pmid: 15350963
references.citation: Blood. 2001 Mar 15;97(6):1679-84
references.pmid: 11238107
references.citation: Lab Invest. 2000 Dec;80(12):1819-31
references.pmid: 11140695
references.citation: J Trauma. 1997 Jun;42(6):1101-7
references.pmid: 9210549
references.citation: Exp Cell Res. 2008 Nov 15;314(19):3466-77
references.pmid: 18824167
references.citation: Neurology. 1954 Sep;4(9):674-81
references.pmid: 13214267
references.citation: J Neurotrauma. 2003 Sep;20(9):795-825
references.pmid: 14577860
references.citation: Vascul Pharmacol. 2002 Jun;38(6):323-37
references.pmid: 12529927
references.citation: Clin Dev Immunol. 2008;2008:384982
references.pmid: 18320011
references.citation: J Cell Sci. 2008 Jul 1;121(Pt 13):2115-22
references.pmid: 18565824
references.citation: Biophysik. 1966;3(2):174-80
references.pmid: 5982794
references.citation: J Neurotrauma. 2012 Jan 1;29(1):19-31
references.pmid: 21988198
references.citation: J Neurotrauma. 2013 Oct 1;30(19):1652-63
references.pmid: 23581482
references.citation: Stapp Car Crash J. 2007 Oct;51:17-80
references.pmid: 18278591
references.citation: Am J Physiol Heart Circ Physiol. 2000 Feb;278(2):H469-76
references.pmid: 10666077
references.citation: Exp Cell Res. 2005 Mar 10;304(1):40-9
references.pmid: 15707572
references.citation: Neuroscience. 1998 Oct;86(4):1245-57
references.pmid: 9697130
references.citation: J Neurotrauma. 2009 Dec;26(12):2257-67
references.pmid: 19604096
references.citation: Lymphat Res Biol. 2009 Dec;7(4):229-37
references.pmid: 20143922
references.citation: Curr Eye Res. 2004 Jun;28(6):391-8
references.pmid: 15512946
references.citation: J Trauma. 1994 Sep;37(3):347-57
references.pmid: 8083892
references.citation: Annu Rev Biomed Eng. 2000;2:55-81
references.pmid: 11701507
references.citation: J Membr Biol. 2002 Jul 15;188(2):151-62
references.pmid: 12172640