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Effects of free radicals on permeability and vasomotor response of cerebral vessels

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Summary

To obtain further evidence on the role of free radicals as mediators of secondary brain damage, blood-brain barrier (BBB) function and vasomotor response of pial vessels were studied during cortical superfusion of a free radical-generating system of xanthine-oxidase (XO) and hypoxanthine (HX). Intravenously administered Na+-fluorescein (mol. wt. 376), or fluorescein isothiocyanate (FITC)-dextran (mol. wt. 62,000) served as low- and high-molecular weight BBB indicators. Since undialyzed XO considerably increased the osmolarity of artificial cerebrospinal fluid, XO was subjected to equilibrium dialysis, which did not affect enzyme activity. Cortical superfusion with either HX (4 mM) or dialyzed XO alone (0.5 U/ml; osmolarity, 310 mosmol/l) did not induce a vasomotor response. Cortical superfusion with the free radical-generating system under normotonic conditions (HX plus dialyzed XO), led to moderate arterial dilation only with a maximum of +13%. The venous diameters remained unaffected. Moderate extravasation of the low molecular weight indicator Na+-fluorescein was seen in only 33% of the experiments, leakage of FITC-dextran was never observed. To assess the role of hypertonicity of the superfusate, the same experiments were performed with undialyzed XO. When superfusing the cortex with undialyzed XO (0.5 U/ml; osmolarity, 420 mosmol/l), the pial arteries dilated to 146%–168% of normal. Similarly, simultaneous superfusion with undialyzed XO (0.25 U/ml) and HX (2 mM) elicited arterial dilatation to 161%–178% of normal. Even the pial veins were significantly dilated to 108% of normal. In this series a moderate extravasation of Na+-fluorescein occurred in 75%, with leakage of FITC-dextran in 25%. These findings do not support the concept that oxygen-derived free radicals have a marked effect on normal cerebral vessels. Free radicals cause only a moderate arterial dilation and BBB dysfunction when compared to other mediators of secondary brain damage.

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Correspondence to A. Unterberg.

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Supported by Deutsche Forschungsgemeinschaft: Ba 452/6-5 and Wa 441/2-4

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Unterberg, A., Wahl, M. & Baethmann, A. Effects of free radicals on permeability and vasomotor response of cerebral vessels. Acta Neuropathol 76, 238–244 (1988). https://doi.org/10.1007/BF00687770

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Key words

  • Blood-brain barrier
  • Intravital fluorescence microscopy
  • Oxygen-derived free radicals
  • Xanthine-oxidase/hypoxanthine
  • Pial vessels