Combined effect of alpha1 (cirazoline) and alpha2 (clonidine) adrenergic receptor agonists on I-PGUS transport across the BBB.

<p>Neither drug alone affected I-PGUS uptake, but combined they effectively increased transport across the BBB. ***p<0.001 in comparison to control; n = 12/group.</p

Blood-brain barrier disruption and brain pharmacokinetics of PGUS at two doses of epinephrine.

<p>(A) shows that the 120 nmol/mouse dose of epinephrine decreased the vascular space of I-Alb. (B) shows that neither dose disrupted the BBB. (C) shows that both doses reduced vascular space of I-PGUS and that the 120 nmol/mouse dose also slowed clearance from blood. (D) shows that I-PGUS did not cross the BBB, but that both doses of epinephrine induced transport of I-PGUS across the BBB. n = 7/group.</p

Expression of M6P receptor on nonpermeablized primary monolayer cultures of mouse brain endothelial cells.

<p>Receptor was detected on cells not treated with epinephrine and treatment did not enhance intensity of staining.</p

Effect of adrenergic antagonists on epinephrine-induced uptake of I-PGUS across the BBB.

<p>Upper panel shows that more general alpha, alpha1, and alpha2 antagonists but not beta antagonists blocked epinephrine’s effect. Lower panel shows results that the highly selective alpha1 adrenergic receptor antagonist benoxathian but not the highly selective beta adrenergic receptor antagonist CPG20712A blocked the effect of epinephrine. **p<0.01 and ***p<0.001 inc comparison to control; ##p<0.01 and ###p<0.001 in comparison to epinephrine.</p

Effect of monoamines and acetylcholine on I-PGUS uptake.

<p><b>Only epinephrine enhanced BBB penetration.</b> **P<0.01; n = 7-10/group.</p

Dose response curve for clonidine: Effect on I-PGUS BBB transport.

<p>A high dose of clonidine enhanced I-PGUS transport without disrupting the BBB. *p<0.05 in comparison to control; n = 10/group.</p

Effects of adrenergic antagonists on epinephrine-induced BBB disruption.

<p>Blockade of alpha2 (yohimbine) and beta (propranolol) but not of alpha1 (benoxathian) receptors prevented epinephrine-induced BBB disruption. *p<0.05 in comparison to Control; **p<0.01 in comparison to control; #p<0.05 in comparison to epinepthrine; n = 8/group.</p