Astroglial and vascular interactions of noradrenaline terminals in the rat cerebral cortex

Noradrenaline (NA) has been shown to influence astrocytic and vascular functions related to brain homeostasis, metabolism, local blood flow, and blood-brain barrier permeability. In the current study, we investigate the possible associations that exist between NA-immunoreactive nerve terminals and astrocytes and intraparenchymal blood vessels in the rat frontoparietal cortex, both at the light and electron microscopic levels. As a second step, we sought to determine whether the NA innervation around intracortical microvessels arises from peripheral or central structures by means of injections of N-(2-chloroethyl-N-ethyl-2-bromobenzylamine) (DSP-4), a neurotoxin that specifically destroys NA neurons from the locus ceruleus. At the light microscopic level, 6.8% of all NA-immunoreactive nerve terminals in the frontoparietal cortex were associated with vascular walls, and this perivascular noradrenergic input, together with that of the cerebral cortex, almost completely disappeared after DSP-4 administration. When analyzed at the ultrastructural level in control rats, NA terminals in the neuropil had a mean surface area of 0.53 +/- 0.03 micron2 and were rarely junctional (synaptic incidence close to 7%). Perivascular terminals (located within a 3-micron perimeter from the vessel basal lamina) counted at the electron microscopic level represented 8.8% of the total NA terminals in the cortical tissue. They were smaller (0.29 +/- 0.01 micron2, P < 0.05) than their neuronal counterparts and were located, on average, 1.34 +/- 0.08 microns away from intracortical blood vessels, which consisted mostly of capillaries (65%). None of the perivascular NA terminals engaged in junctional contacts with surrounding neuronal or vascular elements. The primary targets of both neuronal and perivascular NA nerve terminals consisted of dendrites, nerve terminals, astrocytes, and axons, whereas in the immediate vicinity (0.25 micron or less) of the microvessels, astrocytic processes represented the major target. The results of the current study show that penetrating arteries and intracortical microvessels receive a central NA input, albeit parasynaptic in its interaction, originating from the locus ceruleus. Particularly, they point to frequent appositions between both neuronal and perivascular NA terminals and astroglial cells and their processes. Such NA neuronal-glial and neuronal-glial-vascular associations could be of significance in the regulation of local metabolic and vascular functions under normal and pathologic situations.