Journal of Cerebral Blood Flow & Metabolism (1997) 17, 894–904;
doi:10.1097/00004647-199708000-00008
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 m2 and were rarely junctional (synaptic incidence close to 7%). Perivascular
terminals (located within a 3-m 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 m2, P < 0.05) than their neuronal counterparts and were
located, on average, 1.34 0.08 m 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 m 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.
