Mannitol derivate used as a marker for voltammetrically monitored transport across the blood-brain barrier under condition of locus coeruleus stimulation.

1-Deoxy-1-nitro-D-mannitol (DN-Man) was used (femoral vein injection, approximate concentration in the blood 30 mmol.l-1) in pentobarbital anaesthetized rats as a promising marker detectable by differential pulse voltammetry (DPV) to study its transport across the blood-brain barrier (BBB) to the extra-cellular space of the frontoparietal cortex. DN-Man detection limit in in vitro calibrations (saline, blood) using DPV and carbon fiber microelectrodes was 0.5 mmol.l-1 with a good linearity (r = = 0.996) over the entire tested range (up to 30 mmol.l-1). The slow time-course of the rise of DN-Man signal (y = 106/(1 + (17.8/t)3)) in the cortex confirmed the functional BBB state. Electrical stimulation of the locus coeruleus (LC) (300 rectangular pulses at a frequency of 100 Hz, 1 mA, pulse duration 0.2 ms) elevated significantly DN-Man current in the cortex (to 168 +/- 59% of the control, mean +/- S.D., n = 8). The evoked permeation increase of the BBB to DN-Man was short-lasting (minutes), and the second LC stimulation (repeated 5 min after the first one) was ineffective. This fact was probably due to the reduction of DN-Man levels in blood and/or an altered response of microvessels to neurotransmitters. It was shown here that, under carefully controlled surgical and experimental conditions, DPV and DN-Man might be useful for the monitoring of the regional dynamics of BBB transport changes. The presented results also support the view that BBB transport can be influenced by LC neuronal activity.