Brain-blood barrier? Yes and no.

Abstract

Ventriculo-cisternal perfusion of horseradish peroxidase (HRP) in the mousebrainhas demonstrated thata brainblood barrier exists at the microvascular endothelium in brain parenchyma but not in the median eminence of the hypothalamus. The brain-blood barrier is similar to the blood-brain barrier in that: tight junctions prevent the movement of protein between endothelial cells, HRP taken into the endothelial cells is directed to lysosomal dense bodies, and, contrary to the literature, a vesicular transendothelial transport of HRP from brain to blood does not occur under normal conditions. The endocytosis of ventricular injected HRP from the abluminal side of the endothelium is demonstrably less than the endocytosis of intravenous injected HRP from the luminal side; hence, the cerebral endothelium expresses a degree of polarity regarding the internalization of its cell surface membrane and extracellular protein. The passage of cerebrospinal fluid-borne or blood-borne HRP between some ependymal cells of the median eminence is not precluded by tight junctions. These patent extracellular channels offer a direct pathway for the exchange of substances between cerebrospinal fluid in the third ventricle and fenestrated capillaries in the median eminence.Specific morphological characteristics of cerebral endothelial cells and enzyme activities within these cells define the mammalian blood-brain barrier (1-3). The transcellular transport of large molecular weight, blood-borne substances through the endothelium to the brain extracellular space is believed not to occur under normal conditions. Circumventricular organs (i.e., median eminence, area postrema, etc.) and the choroid plexus possess fenestrated capillaries and lie outside the blood-brain barrier (4, 5); circumferential belts of tight junctions between ependymal cells and between choroid epithelial cells lining the circumventricular organs and choroid plexus, respectively, are considered to provide the physical barrier between the blood and cerebrospinal fluid (CSF) (1, 4, 6). Despite the overwhelming acceptance of a blood-brain barrier, available evidence indicates that the cerebral microvasculature does not manifest a brain-blood barrier. The cerebral endothelium is reported to take up protein from the perivascular space and transport it to the luminal surface where the protein is deposited into the blood (7,8). In this fashion the transendothelial transport of protein from brain to blood could supplement the CSF in the removal of substances from the brain extracellular space.Evidence obtained with horseradish peroxidase (HRP) as a tracer is presented in this paper to suggest that a brain-blood barrier exists at the level of capillaries and arterioles in the brain but not in the median eminence of the hypothalamus. Open junctions observed between some median eminence ependymal cells permit the bidirectional exchange of substances between the median eminence capillaries and the third ventricle CSF.MATERIALS AND METHODS The microvascular endothelium and th...

Cytokine signals propagate through the brain

“…62 The ependymal cell layer lining two other CVOs, the median eminence and area postrema, does not form a tight blood-cerebrospinal fluid (CSF) barrier. [63][64][65] This implies that cytokines synthesized and released in these CVOs have access to ventricular CSF. In accordance with this prediction, bioactive IL-1 appears in ventricular CSF after peripheral IL-1 or LPS injection.…”

“…57 IL-1 may get into the ventricular CSF from AP and median eminence because these areas lack tight blood-CSF barrier. [63][64][65] Indeed, bioactive IL-1 appears in CSF after ip injection of LPS. 67 Once in the CSF, it may diffuse by the flow generated by CSF production in the choroid plexus and absorption in the superior saggital sinus.…”

Contrasting effects of nitric oxide on food intake and GH secretion stimulated by a GH-releasing peptide

“…However, though inferentially, such a possibility is supported by many studies on the neuroendocrine effects of these compounds (38±43) and the lack of BBB in some brain areas, namely at the pituitary±medio-basal±hypothalamic level (44).…”

Transcytotic pathway for blood-borne protein through the blood-brain barrier.

“…Protein tracers exposed to the abluminal surface of the cerebral endothelium by way of the blood through the meninges in the mouse, by ruptured interendothelial tight junctions, or by ventriculo-cisternal perfusion of the proteins are not endocytosed demonstrably by the endothelium but fill stationary pits and invaginations in the abluminal surface (9,(11)(12)(13). We speculated that the abluminal pits are misinterpreted by others as vesicles participating in transendothelial transport bidirectionally through the cerebral endothelium (11,13). A similar interpretation is available for endothelial cells in peripheral tissues (14).…”