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Cyclooxygenase Inhibition Limits Blood-Brain Barrier Disruption following Intracerebral Injection of Tumor Necrosis Factor-alpha in the Rat

Candelario-Jalil, Dr. Eduardo and Taheri, Dr. Saeid and Yang, Dr. Yi and Sood, Dr. Rohit and Grossetete, Dr. Mark and Estrada, Eduardo and Fiebich, Dr. Bernd L. and Rosenberg, Dr. Gary A. (2007) Cyclooxygenase Inhibition Limits Blood-Brain Barrier Disruption following Intracerebral Injection of Tumor Necrosis Factor-alpha in the Rat. [Journal (Paginated)]

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Abstract

Increased permeability of the blood-brain barrier (BBB) is important in neurological disorders. Neuroinflammation is associated with increased BBB breakdown and brain injury. Tumor necrosis factor-alpha (TNF-a) is involved in BBB injury and edema formation through a mechanism involving matrix metalloproteinase (MMP) upregulation. There is emerging evidence indicating that cyclooxygenase (COX) inhibition limits BBB disruption following ischemic stroke and bacterial meningitis, but the mechanisms involved are not known. We used intracerebral injection of TNF-a to study the effect of COX inhibition on TNF-a-induced BBB breakdown, MMP expression/activity and oxidative stress. BBB disruption was evaluated by the uptake of 14C-sucrose into the brain and by magnetic resonance imaging (MRI) utilizing Gd-DTPA as a paramagnetic contrast agent. Using selective inhibitors of each COX isoform, we found that COX-1 activity is more important than COX-2 in BBB opening. TNF-a induced a significant upregulation of gelatinase B (MMP-9), stromelysin-1 (MMP-3) and COX-2. In addition, TNF-a significantly depleted glutathione as compared to saline. Indomethacin (10 mg/kg; i.p.), an inhibitor of COX-1 and COX-2, reduced BBB damage at 24 h. Indomethacin significantly attenuated MMP-9 and MMP-3 expression and activation, and prevented the loss of endogenous radical scavenging capacity following intracerebral injection of TNF-a. Our results show for the first time that BBB disruption during neuroinflammation can be significantly reduced by administration of COX inhibitors. Modulation of COX in brain injury by COX inhibitors or agents modulating prostaglandin E2 formation/signaling may be useful in clinical settings associated with BBB disruption.

Item Type:Journal (Paginated)
Keywords:cyclooxygenase-2; COX-2; COX-1; prostaglandin E2; neuroinflammation; blood-brain barrier; ischemia; stroke; matrix metalloproteinase; MMP-3; MMP-9; gelatinase B; stromelysin-1; oxidative stress; indomethacin; cyclooxygenase-1; glutathione; free radicals; MRI
Subjects:Neuroscience > Neurology
Neuroscience > Neuropharmacology
Neuroscience > Brain Imaging
Neuroscience > Neurochemistry
ID Code:5832
Deposited By: Candelario-Jalil, Dr Eduardo
Deposited On:22 Nov 2007 01:49
Last Modified:11 Mar 2011 08:57

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References

Akundi RS, Candelario-Jalil E, Hess S, Hull M, Lieb K, Gebicke-Haerter PJ and Fiebich BL (2005b) Signal transduction pathways regulating cyclooxygenase-2 in lipopolysaccharide-activated primary rat microglia. Glia 51:199-208.

Akundi RS, Candelario-Jalil E, Hess S, Hull M, Lieb K, Gebicke-Haerter PJ and Fiebich BL (2005a) Signal transduction pathways regulating cyclooxygenase-2 in lipopolysaccharide-activated primary rat microglia. Glia 51:199-208.

Badie B, Schartner JM, Hagar AR, Prabakaran S, Peebles TR, Bartley B, Lapsiwala S, Resnick DK and Vorpahl J (2003) Microglia cyclooxygenase-2 activity in experimental gliomas: possible role in cerebral edema formation. Clin Cancer Res 9:872-877.

Candelario-Jalil E, Gonzalez-Falcon A, Garcia-Cabrera M, Alvarez D, Al-Dalain S, Martinez G, Leon OS and Springer JE (2003a) Assessment of the relative contribution of COX-1 and COX-2 isoforms to ischemia-induced oxidative damage and neurodegeneration following transient global cerebral ischemia. J Neurochem 86:545-555.

Candelario-Jalil E, Gonzalez-Falcon A, Garcia-Cabrera M, Alvarez D, Al-Dalain S, Martinez G, Leon OS and Springer JE (2003b) Assessment of the relative contribution of COX-1 and COX-2 isoforms to ischemia-induced oxidative damage and neurodegeneration following transient global cerebral ischemia. J Neurochem 86:545-555.

Candelario-Jalil E, Gonzalez-Falcon A, Garcia-Cabrera M, Alvarez D, Al-Dalain S, Martinez G, Leon OS and Springer JE (2003c) Assessment of the relative contribution of COX-1 and COX-2 isoforms to ischemia-induced oxidative damage and neurodegeneration following transient global cerebral ischemia. J Neurochem 86:545-555.

Candelario-Jalil E, Gonzalez-Falcon A, Garcia-Cabrera M, Alvarez D, Al-Dalain S, Martinez G, Leon OS and Springer JE (2003d) Assessment of the relative contribution of COX-1 and COX-2 isoforms to ischemia-induced oxidative damage and neurodegeneration following transient global cerebral ischemia. J Neurochem 86:545-555.

Candelario-Jalil E, Gonzalez-Falcon A, Garcia-Cabrera M, Leon OS and Fiebich BL (2007c) Post-ischaemic treatment with the cyclooxygenase-2 inhibitor nimesulide reduces blood-brain barrier disruption and leukocyte infiltration following transient focal cerebral ischaemia in rats. J Neurochem 100:1108-1120.

Candelario-Jalil E, Gonzalez-Falcon A, Garcia-Cabrera M, Leon OS and Fiebich BL (2007e) Post-ischaemic treatment with the cyclooxygenase-2 inhibitor nimesulide reduces blood-brain barrier disruption and leukocyte infiltration following transient focal cerebral ischaemia in rats. J Neurochem 100:1108-1120.

Candelario-Jalil E, Gonzalez-Falcon A, Garcia-Cabrera M, Leon OS and Fiebich BL (2007d) Post-ischaemic treatment with the cyclooxygenase-2 inhibitor nimesulide reduces blood-brain barrier disruption and leukocyte infiltration following transient focal cerebral ischaemia in rats. J Neurochem 100:1108-1120.

Candelario-Jalil E, Gonzalez-Falcon A, Garcia-Cabrera M, Leon OS and Fiebich BL (2007a) Post-ischaemic treatment with the cyclooxygenase-2 inhibitor nimesulide reduces blood-brain barrier disruption and leukocyte infiltration following transient focal cerebral ischaemia in rats. J Neurochem 100:1108-1120.

Candelario-Jalil E, Gonzalez-Falcon A, Garcia-Cabrera M, Leon OS and Fiebich BL (2007b) Post-ischaemic treatment with the cyclooxygenase-2 inhibitor nimesulide reduces blood-brain barrier disruption and leukocyte infiltration following transient focal cerebral ischaemia in rats. J Neurochem 100:1108-1120.

Candelario-Jalil E, Gonzalez-Falcon A, Garcia-Cabrera M, Leon OS and Fiebich BL (2007f) Post-ischaemic treatment with the cyclooxygenase-2 inhibitor nimesulide reduces blood-brain barrier disruption and leukocyte infiltration following transient focal cerebral ischaemia in rats. J Neurochem 100:1108-1120.

Cipollone F, Fazia ML, Iezzi A, Cuccurullo C, De CD, Ucchino S, Spigonardo F, Marchetti A, Buttitta F, Paloscia L, Mascellanti M, Cuccurullo F and Mezzetti A (2005) Association between prostaglandin E receptor subtype EP4 overexpression and unstable phenotype in atherosclerotic plaques in human. Arterioscler Thromb Vasc Biol 25:1925-1931.

de Vries HE, Blom-Roosemalen MC, van OM, de Boer AG, van Berkel TJ, Breimer DD and Kuiper J (1996) The influence of cytokines on the integrity of the blood-brain barrier in vitro. J Neuroimmunol 64:37-43.

Fernandez-Checa JC and Kaplowitz N (1990) The use of monochlorobimane to determine hepatic GSH levels and synthesis. Anal Biochem 190:212-219.

Fiala M, Looney DJ, Stins M, Way DD, Zhang L, Gan X, Chiappelli F, Schweitzer ES, Shapshak P, Weinand M, Graves MC, Witte M and Kim KS (1997) TNF-alpha opens a paracellular route for HIV-1 invasion across the blood-brain barrier. Mol Med 3:553-564.

Fridman R, Toth M, Chvyrkova I, Meroueh SO and Mobashery S (2003b) Cell surface association of matrix metalloproteinase-9 (gelatinase B). Cancer Metastasis Rev 22:153-166.

Fridman R, Toth M, Chvyrkova I, Meroueh SO and Mobashery S (2003a) Cell surface association of matrix metalloproteinase-9 (gelatinase B). Cancer Metastasis Rev 22:153-166.

Gasche Y, Copin JC, Sugawara T, Fujimura M and Chan PH (2001) Matrix metalloproteinase inhibition prevents oxidative stress-associated blood-brain barrier disruption after transient focal cerebral ischemia. J Cereb Blood Flow Metab 21:1393-1400.

Gu Z, Kaul M, Yan B, Kridel SJ, Cui J, Strongin A, Smith JW, Liddington RC and Lipton SA (2002) S-nitrosylation of matrix metalloproteinases: signaling pathway to neuronal cell death. Science 297:1186-1190.

Gurney KJ, Estrada EY and Rosenberg GA (2006b) Blood-brain barrier disruption by stromelysin-1 facilitates neutrophil infiltration in neuroinflammation. Neurobiol Dis 23:87-96.

Gurney KJ, Estrada EY and Rosenberg GA (2006a) Blood-brain barrier disruption by stromelysin-1 facilitates neutrophil infiltration in neuroinflammation. Neurobiol Dis 23:87-96.

Hawkins BT and Davis TP (2005) The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev 57:173-185.

Hewett SJ, Bell SC and Hewett JA (2006) Contributions of cyclooxygenase-2 to neuroplasticity and neuropathology of the central nervous system. Pharmacol Ther 112:335-357.

Kadurugamuwa JL, Hengstler B and Zak O (1989) Cerebrospinal fluid protein profile in experimental pneumococcal meningitis and its alteration by ampicillin and anti-inflammatory agents. J Infect Dis 159:26-34.

Kamencic H, Lyon A, Paterson PG and Juurlink BH (2000) Monochlorobimane fluorometric method to measure tissue glutathione. Anal Biochem 286:35-37.

Kinugasa Y, Hatori M, Ito H, Kurihara Y, Ito D and Nagumo M (2004) Inhibition of cyclooxygenase-2 suppresses invasiveness of oral squamous cell carcinoma cell lines via down-regulation of matrix metalloproteinase-2 and CD44. Clin Exp Metastasis 21:737-745.

Kyrkanides S, Moore AH, Olschowka JA, Daeschner JC, Williams JP, Hansen JT and Kerry OM (2002) Cyclooxygenase-2 modulates brain inflammation-related gene expression in central nervous system radiation injury. Brain Res Mol Brain Res 104:159-169.

Mark KS, Trickler WJ and Miller DW (2001c) Tumor necrosis factor-alpha induces cyclooxygenase-2 expression and prostaglandin release in brain microvessel endothelial cells. J Pharmacol Exp Ther 297:1051-1058.

Mark KS, Trickler WJ and Miller DW (2001b) Tumor necrosis factor-alpha induces cyclooxygenase-2 expression and prostaglandin release in brain microvessel endothelial cells. J Pharmacol Exp Ther 297:1051-1058.

Mark KS, Trickler WJ and Miller DW (2001a) Tumor necrosis factor-alpha induces cyclooxygenase-2 expression and prostaglandin release in brain microvessel endothelial cells. J Pharmacol Exp Ther 297:1051-1058.

Morin I, Li WQ, Su S, Ahmad M and Zafarullah M (1999) Induction of stromelysin gene expression by tumor necrosis factor alpha is inhibited by dexamethasone, salicylate, and N-acetylcysteine in synovial fibroblasts. J Pharmacol Exp Ther 289:1634-1640.

Nagase H, Fields CG and Fields GB (1994) Design and characterization of a fluorogenic substrate selectively hydrolyzed by stromelysin 1 (matrix metalloproteinase-3). J Biol Chem 269:20952-20957.

Ogata Y, Enghild JJ and Nagase H (1992) Matrix metalloproteinase 3 (stromelysin) activates the precursor for the human matrix metalloproteinase 9. J Biol Chem 267:3581-3584.

Pan MR, Chuang LY and Hung WC (2001) Non-steroidal anti-inflammatory drugs inhibit matrix metalloproteinase-2 expression via repression of transcription in lung cancer cells. FEBS Lett 508:365-368.

Paoletti AM, Piccirilli S, Costa N, Rotiroti D, Bagetta G and Nistico G (1998) Systemic administration of N omega-nitro-L-arginine methyl ester and indomethacin reduces the elevation of brain PGE2 content and prevents seizures and hippocampal damage evoked by LiCl and tacrine in rat. Exp Neurol 149:349-355.

Patlak CS, Blasberg RG and Fenstermacher JD (1983) Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab 3:1-7.

Pavlovic S, Du B, Sakamoto K, Khan KM, Natarajan C, Breyer RM, Dannenberg AJ and Falcone DJ (2006) Targeting prostaglandin E2 receptors as an alternative strategy to block cyclooxygenase-2-dependent extracellular matrix-induced matrix metalloproteinase-9 expression by macrophages. J Biol Chem 281:3321-3328.

Pepicelli O, Fedele E, Berardi M, Raiteri M, Levi G, Greco A, Ajmone-Cat MA and Minghetti L (2005) Cyclo-oxygenase-1 and -2 differently contribute to prostaglandin E2 synthesis and lipid peroxidation after in vivo activation of N-methyl-D-aspartate receptors in rat hippocampus. J Neurochem 93:1561-1567.

Ramilo O, Saez-Llorens X, Mertsola J, Jafari H, Olsen KD, Hansen EJ, Yoshinaga M, Ohkawara S, Nariuchi H and McCracken GH, Jr. (1990) Tumor necrosis factor alpha/cachectin and interleukin 1 beta initiate meningeal inflammation. J Exp Med 172:497-507.

Rosenberg GA, Cunningham LA, Wallace J, Alexander S, Estrada EY, Grossetete M, Razhagi A, Miller K and Gearing A (2001) Immunohistochemistry of matrix metalloproteinases in reperfusion injury to rat brain: activation of MMP-9 linked to stromelysin-1 and microglia in cell cultures. Brain Res 893:104-112.

Rosenberg GA, Estrada EY and Dencoff JE (1998b) Matrix metalloproteinases and TIMPs are associated with blood-brain barrier opening after reperfusion in rat brain. Stroke 29:2189-2195.

Rosenberg GA, Estrada EY and Dencoff JE (1998a) Matrix metalloproteinases and TIMPs are associated with blood-brain barrier opening after reperfusion in rat brain. Stroke 29:2189-2195.

Rosenberg GA, Estrada EY, Dencoff JE and Stetler-Stevenson WG (1995a) Tumor necrosis factor-alpha-induced gelatinase B causes delayed opening of the blood-brain barrier: an expanded therapeutic window. Brain Res 703:151-155.

Rosenberg GA, Estrada EY, Dencoff JE and Stetler-Stevenson WG (1995c) Tumor necrosis factor-alpha-induced gelatinase B causes delayed opening of the blood-brain barrier: an expanded therapeutic window. Brain Res 703:151-155.

Rosenberg GA, Estrada EY, Dencoff JE and Stetler-Stevenson WG (1995b) Tumor necrosis factor-alpha-induced gelatinase B causes delayed opening of the blood-brain barrier: an expanded therapeutic window. Brain Res 703:151-155.

Schmidley JW, Dadson J, Iyer RS and Salomon RG (1992) Brain tissue injury and blood-brain barrier opening induced by injection of LGE2 or PGE2. Prostaglandins Leukot Essent Fatty Acids 47:105-110.

Sood R, Taheri S, Estrada EY and Rosenberg GA (2007b) Quantitative evaluation of the effect of propylene glycol on BBB permeability. J Magn Reson Imaging 25:39-47.

Sood R, Taheri S, Estrada EY and Rosenberg GA (2007a) Quantitative evaluation of the effect of propylene glycol on BBB permeability. J Magn Reson Imaging 25:39-47.

Ting P (1990) Indomethacin attenuates early postischemic vasogenic edema and cerebral injury. Adv Neurol 52:119-126.

Trickler WJ, Mayhan WG and Miller DW (2005) Brain microvessel endothelial cell responses to tumor necrosis factor-alpha involve a nuclear factor kappa B (NF-kappaB) signal transduction pathway. Brain Res 1048:24-31.

Tsao N, Hsu HP, Wu CM, Liu CC and Lei HY (2001) Tumour necrosis factor-alpha causes an increase in blood-brain barrier permeability during sepsis. J Med Microbiol 50:812-821.

Wilhelm SM, Collier IE, Kronberger A, Eisen AZ, Marmer BL, Grant GA, Bauer EA and Goldberg GI (1987) Human skin fibroblast stromelysin: structure, glycosylation, substrate specificity, and differential expression in normal and tumorigenic cells. Proc Natl Acad Sci U S A 84:6725-6729.

Yang GY, Gong C, Qin Z, Liu XH and Lorris BA (1999) Tumor necrosis factor alpha expression produces increased blood-brain barrier permeability following temporary focal cerebral ischemia in mice. Brain Res Mol Brain Res 69:135-143.

Yang Y, Estrada EY, Thompson JF, Liu W and Rosenberg GA (2007) Matrix metalloproteinase-mediated disruption of tight junction proteins in cerebral vessels is reversed by synthetic matrix metalloproteinase inhibitor in focal ischemia in rat. J Cereb Blood Flow Metab 27:697-709.

Zhang JW and Gottschall PE (1997) Zymographic measurement of gelatinase activity in brain tissue after detergent extraction and affinity-support purification. J Neurosci Methods 76:15-20.

Zuckerman SL, Mirro R, Armstead WM, Shibata M and Leffler CW (1994) Indomethacin reduces ischemia-induced alteration of blood-brain barrier transport in piglets. Am J Physiol 266:H2198-H2203.

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