Summary
Although free radical species (ROS; i.e., O -2 , -OH, H2O2) among other mediators, may be involved in altering the blood-brain barrier (BBB), little is known about the endogenous ability of cerebromicrovascular endothelium to generate ROS. This study examines the capacity of rat endothelial cells (RBEC) to produce ROS in normoxia and hypoxia/reoxygenation. Cultured RBEC were exposed to an oxygen-depleted atmosphere (containing 95% N2 and 5% CO2) for 4 hr at 37°C and air (10 min) at room temperature to simulate “ischemia/reperfusion”. Nitroblue tetrazolium (NBT) reduction [formation of nitroblue formazan (NBF)] served as a marker for the production of ROS. The release of lactate dehydrogenase (LDH) and [3H]arachidonic acid (AA) was used to assess cellular integrity. RBEC exposed to hypoxia/reoxygenation produced up to 59% greater NBF formation than controls without affecting the LDH or AA release. The production of ROS was calcium-dependent and not affected by AA or its metabolites. The findings indicate that the RBEC can produce superoxide dismutase (SOD)-inhibita-ble ROS which are augmented by hypoxia/reoxygenation. It is suggested that in vivo cerebromicrovascular endothelium may contribute to the formation of ROS and play a role in ischemic brain edema.
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References
Baehner RL, Boxer LA, Davis J (1976) The biochemical basis of nitroblue tetrazolium reduction in normal human and chronic granulomatous disease polymorphonuclear leukocytes. Blood 48: 309–313
Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA (1990) Apparent hydroxyl radical production by peroxynitrite: Implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA 87: 1620–1624
Chan PH (1989) The role of oxygen radicals in brain injury and edema, Chapter 30. In: Chow CK (ed) Cellular antioxidant defense mechanisms, Vol III. CRC, Boca Raton, Florida, pp 89–109
Chan PH, Schmidley JW, Fishman RA, Longar SM (1984) Brain injury, edema, and vascular permeability changes induced by oxygen-derived free radicals. Neurology 34: 315–320
Halliwell B (1992) Reactive oxygen species and the central nervous system. J Neurochem 59: 1609–1623
Halliwell B (1993) The role of oxygen radicals in human disease, with particular reference to the vascular system. Haemostasis 23 [Suppl 1]: 118–126
Lowry OH, Passonneau JV (1972) A flexible system of enzymatic analysis. Academic Press, New York
McCarron RM, Uematsu S, Merkel N, Long D, Bembry J, Spatz M (1990) The role of arachidonic acid and oxygen radicals on cerebromicrovascular endothelial permeability. Acta Neurochir (Wien) [Suppl] 51: 61–64
Menger MD, Lehr H-A, Messmer K (1991) Role of oxygen radicals in the microcirculatory manifestations of postischemic injury. Klin Wochensehr 69: 1050–1055
Moneada S, Palmer RM, Higgs EA (1991) Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 43:109–142
Mrsulja BB, Djuric BM, Crejic V, Mrsulja BJ, Abe K, Spatz M, Klatzo I (1980) Biochemistry of experimental ischemic edema. Adv Neurol 28: 217–230
Spatz M, Bembry J, Dodson RF, Hervonen H, Murray, MR (1980) Endothelial cell culture derived from isolated cerebral microvessels. Brain Res 191: 577–582
Stanimirovic DB, Bertrand N, McCarron R, Uematsu S, Spatz M (1994) Arachidonic acid release and permeability changes induced by endothelins in human cerebromicrovascular endothelium. Acta Neurochir (Wien) [Suppl] 60: 71–75
Vercellotti GM, Dolson M, Schorer AE, Moldow CR (1988) Endothelial cell heterogeneity: antioxidant profiles detenriine vulnerability to oxidant injury. Proc Soc Exp Biol Med 187: 181–189
Villacara A, Spatz M, Dodson RF, Com C, Bembry J (1989) Effect of arachidonic acid on cultured cerebromicrovascular endothelium: permeability, lipid peroxidation and membrane fluidity. Acta Neuropathol (Berl) 78: 310–316
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© 1997 Springer-Verlag
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Strasser, A., Stanimirovic, D., Kawai, N., McCarron, R.M., Spatz, M. (1997). Hypoxia Modulates Free Radical Formation in Brain Microvascular Endothelium. In: James, H.E., et al. Brain Edema X. Acta Neurochirurgica Supplements, vol 70. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6837-0_3
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DOI: https://doi.org/10.1007/978-3-7091-6837-0_3
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