PMID- 25312844 OWN - NLM STAT- MEDLINE DCOM- 20150212 LR - 20220408 IS - 1879-1883 (Electronic) IS - 0002-9610 (Linking) VI - 208 IP - 6 DP - 2014 Dec TI - Tumor necrosis factor-alpha disruption of brain endothelial cell barrier is mediated through matrix metalloproteinase-9. PG - 954-60; discussion 960 LID - S0002-9610(14)00450-4 [pii] LID - 10.1016/j.amjsurg.2014.08.014 [doi] AB - Traumatic brain injuries cause vascular hyperpermeability. Tumor necrosis factor-alpha (TNF-alpha), matrix metalloproteinase-9 (MMP-9), and caspase-3 may be important in these processes but the relationship between them has not been investigated. We hypothesized that TNF-alpha regulates caspase-3-mediated hyperpermeability and blood brain barrier damage and hyperpermeability directly or indirectly via activation of MMP-9. To test this, rat brain microvascular endothelial cells were treated with TNF-alpha with or without inhibition of MMP-9. Monolayer permeability was measured, zonula occludens-1 and F-actin configuration were examined, and MMP-9 and caspase-3 activities were quantified. TNF-alpha increased monolayer permeability, damaged zonula occludens-1, induced filamentous-actin stress fiber formation, and increased both MMP-9 and caspase-3 activities. Inhibition of MMP-9 attenuated these changes. These data highlight a novel link between TNF-alpha and MMP-9 and show that TNF-alpha regulated caspase-3-mediated hyperpermeability and vascular damage may be linked to MMP-9 in vitro. These findings augment the understanding of traumatic brain injury and pave the way for improved treatment. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Wiggins-Dohlvik, Katie AU - Wiggins-Dohlvik K AD - Department of Surgery, Baylor Scott and White Health, Temple, TX, USA; Department of Surgery, Texas A&M University Health Science Center College of Medicine, Temple, TX, USA. FAU - Merriman, Morgan AU - Merriman M AD - Department of Surgery, Baylor Scott and White Health, Temple, TX, USA; Department of Surgery, Texas A&M University Health Science Center College of Medicine, Temple, TX, USA. FAU - Shaji, Chinchusha A AU - Shaji CA AD - Department of Surgery, Baylor Scott and White Health, Temple, TX, USA; Department of Surgery, Texas A&M University Health Science Center College of Medicine, Temple, TX, USA. FAU - Alluri, Himakarnika AU - Alluri H AD - Department of Surgery, Baylor Scott and White Health, Temple, TX, USA; Department of Surgery, Texas A&M University Health Science Center College of Medicine, Temple, TX, USA. FAU - Grimsley, Marcene AU - Grimsley M AD - Department of Surgery, Baylor Scott and White Health, Temple, TX, USA; Department of Surgery, Texas A&M University Health Science Center College of Medicine, Temple, TX, USA. FAU - Davis, Matthew L AU - Davis ML AD - Department of Surgery, Baylor Scott and White Health, Temple, TX, USA; Department of Surgery, Texas A&M University Health Science Center College of Medicine, Temple, TX, USA. FAU - Smith, Randall W AU - Smith RW AD - Department of Surgery, Baylor Scott and White Health, Temple, TX, USA; Department of Surgery, Texas A&M University Health Science Center College of Medicine, Temple, TX, USA. FAU - Tharakan, Binu AU - Tharakan B AD - Department of Surgery, Baylor Scott and White Health, Temple, TX, USA; Department of Surgery, Texas A&M University Health Science Center College of Medicine, Temple, TX, USA. Electronic address: btharakan@sw.org. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140928 PL - United States TA - Am J Surg JT - American journal of surgery JID - 0370473 RN - 0 (Matrix Metalloproteinase Inhibitors) RN - 0 (TJP1 protein, human) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Zonula Occludens-1 Protein) RN - EC 3.4.22.- (Caspase 3) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM MH - Animals MH - Blood-Brain Barrier/*metabolism MH - Brain/*cytology MH - Brain Injuries/metabolism MH - Caspase 3/metabolism MH - Cells, Cultured MH - Endothelial Cells/metabolism MH - Matrix Metalloproteinase 9/*metabolism MH - Matrix Metalloproteinase Inhibitors/pharmacology MH - Rats MH - Tumor Necrosis Factor-alpha/*metabolism MH - Zonula Occludens-1 Protein/metabolism OTO - NOTNLM OT - Blood brain barrier OT - Caspase-3 OT - Gelatinase B OT - Matrix metalloproteinase OT - Traumatic brain injury OT - Tumor necrosis factor EDAT- 2014/10/15 06:00 MHDA- 2015/02/13 06:00 CRDT- 2014/10/15 06:00 PHST- 2014/03/28 00:00 [received] PHST- 2014/08/20 00:00 [revised] PHST- 2014/08/25 00:00 [accepted] PHST- 2014/10/15 06:00 [entrez] PHST- 2014/10/15 06:00 [pubmed] PHST- 2015/02/13 06:00 [medline] AID - S0002-9610(14)00450-4 [pii] AID - 10.1016/j.amjsurg.2014.08.014 [doi] PST - ppublish SO - Am J Surg. 2014 Dec;208(6):954-60; discussion 960. doi: 10.1016/j.amjsurg.2014.08.014. Epub 2014 Sep 28.