RT Journal Article
T1 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) produces edema due to BBB disruption induced by MMP-9 activation in rat hippocampus
A1 Pérez Hernández, Mercedes
A1 Gutiérrez López, María Dolores
A1 Fernández Valle, María Encarnación
A1 Rubio Araiz, Ana
A1 Vidal Casado, Rebeca
A1 Gutiérrez López, María Dolores
A1 O'Shea Gaya, María Esther
A1 Colado Megías, María Isabel
AB The recreational drug of abuse, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) disrupts blood-brain barrier (BBB) integrity in rats through an early P2X7 receptor-mediated event which induces MMP-9 activity. Increased BBB permeability often causes plasma proteins and water to access cerebral tissue leading to vasogenic edema formation. The current study was performed to examine the effect of a single neurotoxic dose of MDMA (12.5 mg/kg, i.p.) on in vivo edema development associated with changes in the expression of the perivascular astrocytic water channel, AQP4, as well as in the expression of the tight-junction (TJ) protein, claudin-5 and Evans Blue dye extravasation in the hippocampus of adult male Dark Agouti rats. We also evaluated the ability of the MMP-9 inhibitor, SB-3CT (25 mg/kg, i.p.), to prevent these changes in order to validate the involvement of MMP-9 activation in MDMA-induced BBB disruption. The results show that MDMA produces edema of short duration temporally associated with changes in AQP4 expression and a reduction in claudin-5 expression, changes which are prevented by SB-3CT. In addition, MDMA induces a short-term increase in both tPA activity and expression, a serine-protease which is involved in BBB disruption and upregulation of MMP-9 expression. In conclusion, this study provides evidence enough to conclude that MDMA induces edema of short duration due to BBB disruption mediated by MMP-9 activation.
PB Elsevier
SN 0028-3908
YR 2017
FD 2017-05-01
LK https://hdl.handle.net/20.500.14352/112126
UL https://hdl.handle.net/20.500.14352/112126
LA eng
NO Pérez-Hernández M, Fernández-Valle ME, Rubio-Araiz A, Vidal R, Gutiérrez-López MD, O'Shea E, Colado MI. 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) produces edema due to BBB disruption induced by MMP-9 activation in rat hippocampus. Neuropharmacology. 2017 May 15;118:157-166. doi: 10.1016/j.neuropharm.2017.03.019. Epub 2017 Mar 16. PMID: 28322979
NO UCM910258
NO Ministerio de Economía y Competitividad (España)
NO Ministerio de Sanidad, Servicios Sociales e Igualdad (España)
NO Instituto de Salud Carlos III (España)
NO Universidad Complutense de Madrid
NO Comunidad Autónoma de Madrid
DS Docta Complutense
RD 26 dic 2025