Melanin-concentrating hormone (MCH) is a peptide reported to inhibit ACTH and cortisol secretion in teleost fish. Its ability to modify the activity of rat corticotrophs, however, remains controversial. We report here that while the peripheral injection of rat (r) MCH failed to alter plasma ACTH levels of conscious rats with an intact blood-brain barrier (BBB), it significantly activated the hypothalamic-pituitary-adrenocortical axis of rats with increased BBB permeability induced by protamine sulfate administration into the internal carotid artery. Similarly, the intracerebroventricular injection of this peptide into rats with intact BBB measurably released ACTH. The ACTH response to rMCH was markedly, but not totally, inhibited by passive immunoneutralization of CRF. These results indicate that rMCH acts within the central nervous system to stimulate the hypothalamic-pituitary-adrenocortical axis of rats, and that the site of action of the peptide is located in brain structures protected by the BBB. Activation of CRF-secreting neurons represents an important final pathway, although other regulatory factors also seem to be involved.

Brain edema associated with severe chronic hypertension was studied in stroke-prone spontaneously hypertensive rats (SHRSP), 5 to 9 months of age. Blood-brain barrier (BBB) leakage sites and intracerebral spreading pathways for plasma proteins were delineated by an intravenously (i.v.) injected exogenous dye tracer (Evans blue), known to form a complex with albumin in blood, and by immunohistochemical visualization of extravasated endogenous plasma proteins. The tissue content of edema fluid was estimated by measuring the specific gravity of selected brain regions, stained or unstained by the tracer dye, on a bromobenzene-kerosene gradient column. Multifocal BBB leakage sites were macroscopically detected within the cerebral cortex and the deep gray matter after i.v. circulation of Evans blue-albumin for 30 min. After 24 h of i.v. circulation the dye tracer had spread not only locally in the gray matter but also into the adjacent white matter, where it was widely distributed. Immunohistochemically visualized plasma proteins showed similar distribution. Unilateral superior cervical ganglionectomy performed at 4 weeks of age neither increased the incidence of major BBB opening to Evans blue-albumin nor altered the specific gravity of the ipsilateral cerebral hemisphere in grown-up SHRSP, furthermore, the blood pressure remained unchanged. The lack of significant effect on BBB function may possibly be attributed to the extensive reinnervation of the cerebral arteries, verified in the grown-up SHRSP using the Falck-Hillarp fluorescence method for visualization of catecholaminergic nerve fibers. In SHRSP raised on a low-protein and high-salt diet the mean arterial blood pressure was 212 mm Hg compared to 195 mm Hg in controls (P less than 0.05) and the incidence of BBB opening was 72% compared to 25% in controls (P less than 0.05). After 24 h of i.v. circulation of Evans blue-albumin, brain regions stained by the dye tracer showed significantly reduced specific gravity (P less than 0.001), while unstained regions had normal values. Thus the brain edema fluid spread, as revealed by specific gravity measurements, corresponded to the intracerebral distribution of extravasated plasma proteins.

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Delta-sleep-inducing peptide (DSIP), vasoactive intestinal peptide (VIP), peptide YY (PYY) and somatostatin (SOM) were assayed with specific radioimmunological methods in cerebrospinal fluid (CSF) of healthy volunteers, 12 patients with Alzheimer’s disease (AD), 11 patients with multi-infarct dementia (MID) and 10 patients with normal-pressure hydrocephalus (NPH). Patients with NPH were reinvestigated 3 months after a ventriculoperitoneal shunt operation. DSIP, PYY and SOM levels in CSF were decreased in patients with NPH compared to controls. The CSF concentration of SOM was also significantly reduced in patients with AD. No correlations were found between the degree of dementia in any of the illnesses and the CSF concentrations of the peptides. The concentration of DSIP, VIP and SOM increased significantly in parallell to the clinical improvement after the shunt operation in NPH patients.

The aim of the study was to evaluate how implantation of a dialysis probe influences the blood-brain barrier. Leakage of endogenous serum albumin was evaluated by Evans blue/albumin staining and by immunohistochemistry . The passage from blood to dialysate of two substances that normally do not pass into the brain, [3H]inulin and glutamate, was studied 3 and 24 h after insertion of a dialysis probe. Evans blue, given 20 min before rats were killed, was observed around the probe and surrounding brain tissue . Albumin immunoreactivity was seen at considerable distance from the probe with larger spread at 24 h than at 3 h after probe insertion . Glutamate and [3H]inulin were detected in the dialysate with no significant further increase of radioactivity after intracarotid infusion of protamine sulfate that enhances the permeability over the blood-brain barrier. When protamine was followed by infusion of glutamate, the concentrations of taurine increased in the dialysate in four of eight rats . That plasma constituents have access to the brain around the dialysis probe is essential to consider, particularly in studies using substances and drugs that do not pass an intact blood-brain barrier. Key Words: Microdialysis-Blood-brain barrier-Amino acids-Protamine sulfate-Glutamate-Inulin.Abbreviations used : ßBß, blood-brain barrier ; MAP, mean arterial pressure .