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 invest igate the possible associations that exist between NA-immunoreactive n erve terminals and astrocytes and intraparenchymal blood vessels in th e rat frontoparietal cortex, both at the light and electron microscopi c levels. As a second step, we sought to determine whether the NA inne rvation around intracortical microvessels arises from peripheral or ce ntral 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 noradrenerg ic input, together with that of the cerebral cortex, almost completely disappeared after DSP-4 administration. When analyzed at the ultrastr uctural level in control rats, NA terminals in the neuropil had a mean surface area of 0.53 +/- 0.03 mu m(2) and were rarely junctional (syn aptic incidence close to 7%). Perivascular terminals (located within a 3-mu m perimeter from the vessel basal lamina) counted at the electro n microscopic level represented 8.8% of the total NA terminals in the cortical tissue. They were smaller (0.29 +/- 0.01 mu m(2), P < 0.05) t han their neuronal counterparts and were located, on average, 1.34 +/- 0.08 mu m away from intracortical blood vessels, which consisted most ly 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 termi nals consisted of dendrites, nerve terminals, astrocytes, and axons, w hereas in the immediate vicinity (0.25 mu m or less) of the microvesse ls, astrocytic processes represented the major target. The results of the current study show that penetrating arteries and intracortical mic rovessels receive a central NA input, albeit parasynaptic in its inter action, originating from the locus ceruleus. Particularly, they point to frequent appositions between both neuronal and perivascular NA term inals 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.