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The protective influence of the locus ceruleus on the blood‐brain barrier

The functions of the putative noradrenergic innervation of cerebral microvessels from the nucleus locus ceruleus remain ambiguous. Although most evidence indicates that such innervation does not have a major role in the control of cerebral blood flow, there are increasing indications that it modulates transport and permeability functions of the blood‐brain barrier. In this study we investigated the effect of unilateral chemical lesioning of the locus ceruleus on the leakage of radioiodinated human serum albumin across the blood‐brain barrier. Experiments were performed in awake and restrained rats under steady‐state conditions and during drug‐induced systemic arterial hypertension, and in anesthetized and paralyzed rats during bicuculline‐induced seizures. Both hypertension and seizures are known to be associated with increased leakage of macromolecules across the blood‐brain barrier. Albumin leakage into norepinephrine‐depleted forebrain structures ipsilateral to the locus ceruleus lesion was compared with that of the contralateral side. There were no side‐to‐side differences in blood‐brain barrier permeability to albumin under steady‐state conditions, the stress of restraint, or angiotensin‐induced hypertension, or after isoproterenol administration. Norepinephrine‐induced hypertension and seizures, however, caused significant increases in albumin leakage into forebrain structures ipsilateral to the lesion. These results suggest that noradrenergic innervation of cerebral microvessels from the locus ceruleus helps preserve the integrity of the blood‐brain barrier during pathophysiological states associated with hypertension and increased circulating catecholamines.