Lack of effect of topically applied nicotine on pial arteriole diameter and blood-brain barrier integrity in the cat

Abstract

In the present study, the vasomotor effects of nicotine, its interaction with local chemical factors and norepinephrine, and its effects on the permeability of the blood-brain barrier (BBB) were investigated. Using perivascular microapplication, 10(-6) M nicotine was found not to exert a vasomotor effect by itself or to modify the vasodilating effect of an increase in perivascular H+, K+ and adenosine concentration. The constrictor effect of a decrease in H+, K+ or an increase in norepinephrine concentration in the perivascular space was also not altered by 10(-6) M nicotine, indicating a lack of interaction between nicotine and the compounds tested. Using cortical superfusion and intravital fluorescence microscopy nicotine (10(-7) to 10(-3) M) was also found not to affect the diameter of pial arteries during superfusion periods of 30 min each. The integrity of BBB could be demonstrated in time-matched solvent controls over 3 h using intravenously-infused FITC-labelled dextran (MW 70,000) as tracer. During cortical superfusion with 10(-7) to 10(-5) M nicotine the permeability of the BBB was not increased compared with the time-matched controls. However, during superfusion with 10(-4) and 10(-3) M nicotine, tracer extravasation could be quantified by computer-aided image analysis. The extravasation index (EI) increased by up to eight times. These data indicate that only toxic concentrations of nicotine increase BBB permeability to FITC-dextran 70,000.

Chronic nicotine exposure alters blood–brain barrier permeability and diminishes brain uptake of methyllycaconitine

“…However, both acute and chronic in vivo nicotine exposure (at physiologically relevant doses) apparently lacks effect on BBB integrity. Specifically, acute exposure of relevant nicotine doses had little effect on tight junction integrity (Schilling et al . 1992; Chen et al .…”

“…However, both acute and chronic in vivo nicotine exposure (at physiologically relevant doses) apparently lacks effect on BBB integrity. Specifically, acute exposure of relevant nicotine doses had little effect on tight junction integrity (Schilling et al 1992;Chen et al 1995). Similar doses in chronic exposure (> 7 but £ 21 days) did not alter extravasation of macromolecules in human pulmonary epithelium (Minty et al 1984), canine femoral endothelium (Allen et al 1988), hamster cheek pouch microvessels (Myers et al 1988;Mayhan and Sharpe 1998) or rabbit aortic endothelium (although increased microvilli formation and localized areas of 'ruffled' endothelium were noted morphologically) (Booyse et al 1981).…”

The Effects of Psychostimulant Drugs on Blood Brain Barrier Function and Neuroinflammation

“…This BBB disruption occurred as early as 2 h after acute nicotine and after 6 weeks of chronic exposure (Lin et al, 1992; Uzum et al, 1999; Venisnik, 2000;Hawkins et al, 2004, 2005). In vitro studies using either brain microvascular endothelial cells alone or in combination with C6 astrocytes revealed increases of FITC-Dextran and [ 14 C]sucrose leakage across the cells after nicotine treatment (Schilling et al, 1992; Abbruscato et al, 2002). Nicotine also decreases transendothelial electrical resistance in an in vitro BBB model (Hutamekalin et al, 2008; Rodriguez-Gaztelumendi et al, 2011).…”

“… 1 Rodriguez-Gaztelumendi et al (2011); 2 Hutamekalin et al (2008); 3 Schilling et al (1992); 4 Abbruscato et al (2002); 5 Chen et al (2002); 6 Albaugh et al (2004); 7 Speer et al (2002); 8 Manda et al (2010a,b); 9 Liou et al (2007); 10 Yang et al (2006); 11 Paulson et al (2006); 12 Abbruscato et al (2004); 13 Hawkins et al (2005); 14 Uzum et al (1999); 15 Lin et al (1992); 16 Wang et al (1997); 17 Paulson et al (2010); 18 Bradford et al (2011); 19 Canis et al (2009); 20 Lockman et al (2005); 21 Wang et al (1994); 22 Gerzanich et al (2003); 23 Yong et al (1997) .…”

Effect of nicotine and polyaromtic hydrocarbons on cerebral endothelial cells

“…This is probably due to the fact that different aspects of junctional permeability are regulated by distinct mechanisms. Furthermore, an in vivo study has shown that only toxic concentrations of nicotine (10 À4 e 10 À3 M) were able to increase the permeability to 70 kDa FITC-dextran (Schilling et al, 1992).…”