Posttraumatic Invasion of Monocytes across the Blood—Cerebrospinal Fluid Barrier

The invasion of inflammatory cells occurring after ischemic or traumatic brain injury (TBI) has a detrimental effect on neuronal survival and functional recovery after injury. We have recently demonstrated that not only the blood-brain barrier, but also the blood-cerebrospinal fluid (CSF) barrier (BCSFB), has a role in posttraumatic recruitment of neutrophils. Here, we show that TBI results in a rapid increase in synthesis and release into the CSF of a major chemoattractant for monocytes, CCL2, by the choroid plexus epithelium, a site of the BCSFB. Using an in vitro model of the BCSFB, we also show that CCL2 is released across the apical and basolateral membranes of the choroidal epithelium, a pattern of chemokine secretion that promotes leukocyte migration across epithelial barriers. Immunohistochemical and electron microscopic analyses of choroidal tissue provide evidence for the movement of monocytes, sometimes in tandem with neutrophils, along the paracellular pathways between adjacent epithelial cells. These data further support the pathophysiological role of BCSFB in promoting the recruitment of inflammatory cells to the injured brain.

Symptomatic intraventricular xanthogranulomas

This article reviews symptomatic intraventricular xanthogranulomas, based on a case presentation. Bilateral xanthogranulomas of the choroid plexus were removed surgically from the lateral ventricles of a 12-year-old boy. At 9 years of age, he had evidence of increased intracranial pressure and was hospitalized. Dense enhancing masses were detected in computerized tomogram (CT) brain scan. The lesions were in the region of trigones with extension into the temporal horns and into the right occipital horn. The masses were brightly yellow and greasy. They measured 8.5 x 5.5 x 3.5 cm and 10 x 6.5 x 4.5 cm, respectively, and proved to be xanthogranulomas. Review of 35 reported symptomatic intraventricular xanthogranulomas revealed 11 lesions in the lateral ventricles in which six of them were bilateral. Twenty-two lesions were in the third ventricle, and two lesions were in the fourth ventricle. The lesion shows no significant sexual predilection. The patients’ average age is 37.6 years for males, 32.4 years for females, and 34.3 years for both sexes. The size of symptomatic lesions ranged from 1 to 3 cm in diameter but a few were large, up to 8 to 10 cm. The origin of foamy (xanthoma) cells in the xanthogranulomas arising in the choroid plexus is thought to be multicentric including the choroidal epithelium and stromal arachnoidal cells that have undergone xanthomatous changes. Increased intracranial pressure is the significant clinical feature of the intraventricular xanthogranulomas as in other mass lesions within the skull. Surgical extirpation is the treatment of choice if the lesion is accessible and the patient’s general condition is suitable.

Choline uptake across the ventricular membrane of neonate rat choroid plexus

The uptake of [3H]choline from the cerebrospinal fluid (CSF) side of the rat neonatal choroid plexus was characterized in primary cultures of the choroidal epithelium grown on solid supports. Cell-to-medium concentration ratios were ∼5 at 1 min and as high as 70 at 30 min. Apical choline uptake was facilitated; the K m was ∼50 μM. Several organic cations (e.g., hemicholinium-3 and N 1-methylnicotinamide) inhibited uptake. The reduction or removal of external Na+ or the addition of 5 mM LiCl had no effect on uptake. However, increasing external K+ concentration from 3 to 30 mM depolarized ventricular membrane potential (−70 to −15 mV) and reduced uptake to 45% of that for the control. Treatment with 1 mM ouabain or 2 mM BaCl2 reduced uptake 45%, and intracellular acidification reduced uptake to ∼90% of that for controls. These data indicate that the uptake of choline from CSF across the ventricular membrane of the neonatal choroidal epithelium is not directly coupled to Na+ influx but is sensitive to plasma membrane electrical potential.

Cytochemical Localization of Ouabain-sensitive, K+-dependent p-Nitrophenylphosphatase Activity in the Choroid Plexus of Normal and Reserpinized Guinea Pigs

SUMMARY High doses of reserpine induce depletion of biogenic amines. The K-NPPase activity of choroid plexus was determined after one-shot reserpine administration using cerium-based cytochemistry. In normal untreated animals, reaction product was found on the microvilli of the choroidal epithelium but was almost undetectable 3 and 7 days after reserpinization. At 20 days after reserpinization, however, it was detectable. These findings suggested that reserpine decreased the choroidal Na,K-ATPase activity, and that catecholamines might be essential to maintain normal choroidal Na,K-ATPase activity.

Postnatal developmental changes in blood flow to choroid plexuses and cerebral cortex of the rat

Postnatal developmental changes in blood flow to choroid plexuses of the lateral (LVCP) and fourth (4VCP) ventricles and cerebral cortex were studied in pentobarbital-anesthetized rats at 2, 3, 5, and 7-8 wk. Blood flow was measured by indicator fractionation with N-isopropyl-p-[125I]iodoamphetamine as the marker. Blood flow to the LVCP and 4VCP was 2.5 +/- 0.1 and 2.7 +/- 0.1 ml.g-1.min-1, respectively, and did not change between the 2nd and 3rd wk. However, it increased by 34% between the 3rd and 5th wk. From the age of 5 wk on, 4VCP was characterized by higher blood flow rates than LVCP. Cerebral cortical blood flow gradually increased between the 2nd and 5th wk. There was no difference in cortical blood flow between 5-wk-old and adult animals. The changes in choroidal blood flow likely represent a continuing adjustment of the choroidal vascular system to steadily increasing secretory capabilities of the maturing choroidal epithelium.

Na(+)-H+ exchange in choroid plexus and CSF in acute metabolic acidosis or alkalosis

Basolateral Na(+)-H+ exchange was analyzed with an in vivo model of choroid plexus (CP) epithelium in nephrectomized adult rats anesthetized with ketamine. Acid-base balance in blood was altered for 1 h over a pH continuum of 7.19 to 7.53 by equimolar intraperitoneal injections of HCl, NH4Cl, NaCl, or NaHCO3. Compartmental analysis enabled determination of CP intracellular pH (pHi) [dimethadione (DMO) method] and the choroid cellular concentration of 23Na (stable) and 22Na (tracer). HCl acidosis reduced the outwardly directed transmembrane basolateral H+ gradient, lowered the [23Na]i by 25%, and decreased the influx coefficient (Kin) for 22Na from blood into CP parenchyma (by 45% from 0.211 to 0.117 ml.g-1.h-1) and into cerebrospinal fluid (CSF) (by 43%, from 0.897 to 0.516). Compared with acid-loaded rats (HCl or NH4Cl), the NaHCO3-alkalotic animals had significantly enhanced uptake of 22Na into the CP-CSF system. This pH-dependent transport of Na+ from blood to CP was abolished by pretreatment with amiloride, an inhibitor of Na(+)-H+ exchange. Except in severe acidosis (HCl), the choroid cell pHi (7.05 +/- 0.02 in NaCl controls) and [HCO3-] (11-12 mM) remained stable in the face of acidemic and alkalemic challenges. With respect to reaction of the blood-CSF barrier to plasma acid-base perturbations, the responses of the fourth ventricle plexus pHi, [Na+]i, and 22Na uptake were similar to corresponding ones in lateral plexuses. We conclude that in the choroidal epithelium there is a Na(+)-H+ exchange activity capable of modulating Na+ flux into the CSF by approximately 50% as arterial pH is varied from 7.2 to 7.5.

Blood-brain interfaces in vertebrates: a comparative approach

The neuronal microenvironment in the vertebrate brain is isolated from plasma by a series of selective membranes, including the blood-brain barrier, the choroid plexus, and the meningeal barrier. This review deals with the structure and function of these selective membranes in the different vertebrate classes. Present knowledge indicates that all vertebrates have brain barrier membranes and, further, that functional characteristics of these membranes are basically similar in all the vertebrate classes. The blood-brain barrier (or capillary-glial complex) and the meningeal barrier have many of the properties of a tight epithelium, including the presence of tight junctions and specific transport mechanisms. The choroidal epithelium is a typical secretory epithelium. The functional significance of the specialized membranes located at the blood-brain interface is considered, and we suggest that the phylogenetic development of a blood-brain barrier provided neurons of the vertebrate brain with a unique extracellular milieu optimal both for synaptic communication and for nonsynaptic communication via the entire extracellular space.

Vesicular transport of cationized ferritin by the epithelium of the rat choroid plexus.

We have studied the transport of ferritin that was internalized by coated micropinocytic vesicles at the apical surface of the choroid plexus epithelium in situ. After ventriculocisternal perfusion of native ferritin (NF) or cationized ferritin (CF), three routes followed by the tracers are revealed: (a) to lysosomes, (b) to cisternal compartments, and (c) to the basolateral cell surface. (a) NF is micropinocytosed to a very limited degree and appears in a few lysosomal elements whereas CF is taken up in large amounts and can be followed, via endocytic vacuoles and light multivesicular bodies, to dark multivesicular bodies and dense bodies. (b) Occasionally, CF particles are found in cisterns that may represent GERL or trans-Golgi elements, whereas stacked Golgi cisterns never contain CF. (c) Transepithelial vesicular transport of CF is distinctly revealed. The intercellular spaces of the epithelium, below the apical tight junctions, contain numerous clusters of CF particles, often associated with surface-connected, coated vesicles. Vesicles in the process of exocytosis of CF are also present at the basal epithelial surface, whereas connective tissue elements below the epithelium are unlabeled. Our conclusion is that fluid and solutes removed from the cerebrospinal fluid by endocytosis either become sequestered in the lysosomal apparatus of the choroidal epithelium or are transported to the basolateral surface. However, our results do not indicate any significant recycling via Golgi complexes of internalized apical cell membrane.