Histofluorescence study on monoamine entry into the brain before and after opening of the blood-brain barrier by various mechanisms

Abstract

The relationship between exogenous, circulating monoamines to the wall of cerebral microvessels, and the entrance of these amines into the cerebral parenchyma was studied by the formaldehyde histofluorescence technique in rats. No monoamine fluorescence could be detected in the wall tissue of the microvessels (pericytes and andothelial cells) unless either MAO or COMT were inhibited; these are integral to the blood-brain barrier mechanisms to monoamines. After transient opening of the morphologic blood-brain barrier by either a hypertonic of hypertensive insult, the amine fluorescence in the walls of the microvessels was intensified compared to that which was noted after monoamine oxidase inhibition by itself. Following opening of the structural blood-brain barrier, the circulating amines also passed through into the neuropil where they were concentrated within neurons, as demonstrated by prior depletion of endogenous monoamine transmitters by reserpine. Thus, both enzymatic and morphologic mechanisms in the blood-brain barrier ar involved in impeding the passage of monoamines into the cerebral parenchyma.

Functional Heterogeneity of the Cerebrovascular Endothelium

“…3), can be enhanced severalfold in regions where the bar rier has been opened [Hardebo et al, 1977b;Pollay, 1975]. When the BBB is opened experimentally, an accumulation of monoamines in the cells of the microvessel wall is clearly distinguishable by fluores cence microscopy [Hardebo et al, 1979a]. Under these conditions, monoamines may enter the cytoplasm of endothelial cells by pinocytosis, or they may pass be tween or through the endothelial cells to reach the abluminal side of the endothelial membrane and from there enter endothelial cells as well as pericytes.…”

“…Also, intravascular administration of hypertonic so lutions (e.g. urea) opens the BBB and allows large molecules that normally do not penetrate the barrier to pass from blood into brain tissue [Brightman et al, 1973;Edvinsson et al, 1978;Hardebo et al, 1979a]. The hypertonic barrier opening is reversible within a few hours [Hardebo, 1980;Pollay, 1975].…”

“…Only in newborn animals, in which the morphological bar rier is not yet fully developed, has substantial microvascular uptake of circulating neurotransmitter mono amines been demonstrated. In adult animals, with a fully developed morphological BBB, fluorescence microscopy after systemic administration of dopa mine has indicated that the passage of circulating amines is greatly impeded at the luminal surface of the brain [Bertler et al, 1966;Hardebo et al, 1979a].…”

The Blood-Brain Barrier in Acute and Chronic Hypertension

“…Monoamines can, however, be formed in the endothelial cells by decarboxylation of their precursors. The amines are then rapidly inactivated by monoamine oxidase and catechol-a-methyl transferase (80). In the presence of a transitory BBB dysfunction, systemically administered monoaminescan have a profound effect on cerebral metabolism and blood flow (13,81,82).…”

6‐Hydroxydopamine and the blood‐brain barrier in adult conscious rats

“…The passage of 6-OHDA into the brain is not exclusively prevented by the morphological barrier but probably also by the enzymatic barrier to catecholamines in the endothelial cells, i.e. monoamine oxidase and aromatic aminoacid decarboxylase (Bertler et al 1966. Hardebo et al 1979).…”