OBJECTIVE: Traumatic brain injury (TBI) causes an increase in matrix metalloproteinases (MMPs), which are associated with neuroinflammation, blood-brain barrier disruption, hemorrhage, and cell death. We hypothesized that patients with TBI have an increase in MMPs in ventricular cerebrospinal fluid (CSF) and plasma. METHODS: Patients with TBI and a ventricular catheter were entered into the study. Samples of CSF and plasma were collected at the time of catheter placement and at 24 and 72 hours after admission. Seven TBI patients were entered into the study, with 6 having complete data for analysis. Only patients who had a known time of insult that fell within a 6-hour window from initial insult to ventriculostomy were accepted into the study. Control CSF came from ventricular fluid in patients undergoing shunt placement for normal pressure hydrocephalus. Both MMP-2 and MMP-9 were measured with gelatin zymography and MMP-3 with Western immunoblot. RESULTS: We found a significant elevation in the levels of the latent form of MMP-9 (92-kD) in the CSF obtained at the time of arrival (P < 0.05). Elevated levels of MMP-2 were detected in plasma at 72 hours, but not in the CSF. Using albumin from both CSF and blood, we calculated the MMP-9 index, which was significantly increased in the CSF, indicating endogenous MMP production. Western immunoblot showed elevated levels of MMP-3 in CSF at all times measured, whereas MMP-3 was not detected in the CSF of normal pressure hydrocephalus. CONCLUSION: We show that MMPs are increased in the CSF of TBI patients. Although the number of patients was small, the results were robust and clearly demonstrated increases in MMP-3 and MMP-9 in ventricular CSF in TBI patients compared with controls. Although these preliminary results will need to be replicated, we propose that MMPs may be important in blood-brain barrier opening and hemorrhage secondary to brain injury in patients.
OBJECTIVE:Traumatic brain injury (TBI) causes an increase in matrix metalloproteinases (MMPs), which are associated with neuroinflammation, blood-brain barrier disruption, hemorrhage, and cell death. We hypothesized that patients with TBI have an increase in MMPs in ventricular cerebrospinal fluid (CSF) and plasma. METHODS:Patients with TBI and a ventricular catheter were entered into the study. Samples of CSF and plasma were collected at the time of catheter placement and at 24 and 72 hours after admission. Seven TBIpatients were entered into the study, with 6 having complete data for analysis. Only patients who had a known time of insult that fell within a 6-hour window from initial insult to ventriculostomy were accepted into the study. Control CSF came from ventricular fluid in patients undergoing shunt placement for normal pressure hydrocephalus. Both MMP-2 and MMP-9 were measured with gelatin zymography and MMP-3 with Western immunoblot. RESULTS: We found a significant elevation in the levels of the latent form of MMP-9 (92-kD) in the CSF obtained at the time of arrival (P < 0.05). Elevated levels of MMP-2 were detected in plasma at 72 hours, but not in the CSF. Using albumin from both CSF and blood, we calculated the MMP-9 index, which was significantly increased in the CSF, indicating endogenous MMP production. Western immunoblot showed elevated levels of MMP-3 in CSF at all times measured, whereas MMP-3 was not detected in the CSF of normal pressure hydrocephalus. CONCLUSION: We show that MMPs are increased in the CSF of TBIpatients. Although the number of patients was small, the results were robust and clearly demonstrated increases in MMP-3 and MMP-9 in ventricular CSF in TBIpatients compared with controls. Although these preliminary results will need to be replicated, we propose that MMPs may be important in blood-brain barrier opening and hemorrhage secondary to brain injury in patients.
Authors: X Wang; J Jung; M Asahi; W Chwang; L Russo; M A Moskowitz; C E Dixon; M E Fini; E H Lo Journal: J Neurosci Date: 2000-09-15 Impact factor: 6.167
Authors: Anna Rosell; Arantxa Ortega-Aznar; José Alvarez-Sabín; Israel Fernández-Cadenas; Marc Ribó; Carlos A Molina; Eng H Lo; Joan Montaner Journal: Stroke Date: 2006-05-11 Impact factor: 7.914
Authors: Giselli Scaini; Meline O S Morais; Leticia S Galant; Francieli Vuolo; Dhébora M Dall'Igna; Matheus A B Pasquali; Vitor M Ramos; Daniel P Gelain; Jose Claudio F Moreira; Patrícia F Schuck; Gustavo C Ferreira; Francisco G Soriano; Felipe Dal-Pizzol; Emilio L Streck Journal: Mol Neurobiol Date: 2014-01-05 Impact factor: 5.590
Authors: Gail D Anderson; Federico M Farin; Theo K Bammler; Richard P Beyer; Alicia A Swan; Hui-Wen Wilkerson; Eric D Kantor; Michael R Hoane Journal: J Neurotrauma Date: 2011-09-08 Impact factor: 5.269
Authors: Nino Muradashvili; Richard L Benton; Kathryn E Saatman; Suresh C Tyagi; David Lominadze Journal: Metab Brain Dis Date: 2014-04-29 Impact factor: 3.584
Authors: Michael V DeFazio; Richard A Rammo; Jaime R Robles; Helen M Bramlett; W Dalton Dietrich; M Ross Bullock Journal: World Neurosurg Date: 2013-01-08 Impact factor: 2.104