Southwestern Surgical CongressTumor necrosis factor-α disruption of brain endothelial cell barrier is mediated through matrix metalloproteinase-9
Section snippets
Chemicals and reagents
Rat brain microvascular endothelial cells (RBMECs) from Cell Applications, Inc (San Diego, CA), fibronectin from bovine serum (.1% solution; Sigma-Aldrich, St. Louis, MO), RBMEC growth media (Cell Applications, Inc), and Trypsin-EDTA solution (.25%; Invitrogen, Grand Island, NY) were used for all in vitro experiments. TNF-α was obtained from Sigma and MMP-9 inhibitor 1 from Calbiochem (San Diego, CA). DMEM-Fluorobrite (Life Technologies, Grand Island, NY) media and Fluorescein isothiocyanate
Matrix metalloproteinase-9 inhibitor 1 decreases tumor necrosis factor-α-induced monolayer hyperpermeability
Fluorescent intensity was measured and values are expressed as a percentage of control. RBMEC monolayers exposed to TNF-α displayed significantly increased permeability evidenced by increased fluorescent intensity when compared with those measured in the control group (P = .002). MMP-9 inhibitor 1 significantly attenuated this increase (P = .02; Fig. 1).
Tumor necrosis factor-α-induced disruption to tight junction protein zonula occluden-1 is ameliorated with matrix metalloproteinase-9 inhibitor 1
Confocal images of RBMECs with immunofluorescence staining of the endothelial TJ protein ZO-1 are illustrated in Fig. 2A, demonstrating loss
Comments
The complexity of the human brain is paralleled only by the pathology that afflicts it. Traumatic injuries are no exception, and the role of TNF-α therein is equally as complex. As a testament to this, a PubMed query for ‘TNF and brain injury’ returns over 1,000 results. In this literature, TNF-α has been shown, among other things, to stimulate apoptosis of brain microvascular endothelium, increase vasogenic brain edema, and correlate with breakdown of the BBB.7, 23, 24, 26 On the contrary,
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The authors declare no conflicts of interest.
We acknowledge the Office of Academic Operations and Department of Surgery, Baylor Scott & White Health, Temple, Texas, for financial support and Texas A&M Health Science Center College of Medicine Integrated Imaging Laboratory for the use of the confocal laser microscope and technical assistance with imaging.