Abstract
Hydrocephalic hyh mutant mice undergo a programmed loss of the neuroepithelium/ependyma followed by a reaction of periventricular astrocytes, which form a new cell layer covering the denuded ventricular surface. We present a comparative morphological and functional study of the newly formed layer of astrocytes and the multiciliated ependyma of hyh mice. Transmission electron microscopy, immunocytochemistry for junction proteins (N-cadherin, connexin 43) and proteins involved in permeability (aquaporin 4) and endocytosis (caveolin-1, EEA1) were used. Horseradish peroxidase (HRP) and lanthanum nitrate were used to trace the intracellular and paracellular transport routes. The astrocyte layer shares several cytological features with the normal multiciliated ependyma, such as numerous microvilli projected into the ventricle, extensive cell–cell interdigitations and connexin 43-based gap junctions, suggesting that these astrocytes are coupled to play an unknown function as a cell layer. The ependyma and the astrocyte layers also share transport properties: (1) high expression of aquaporin 4, caveolin-1 and the endosome marker EEA1; (2) internalization into endocytic vesicles and early endosomes of HRP injected into the ventricle; (3) and a similar paracellular route of molecules moving between CSF, the subependymal neuropile and the pericapillary space, as shown by lanthanum nitrate and HRP. A parallel analysis performed in human hydrocephalic foetuses indicated that a similar phenomenon would occur in humans. We suggest that in foetal-onset hydrocephalus, the astrocyte assembly at the denuded ventricular walls functions as a CSF–brain barrier involved in water and solute transport, thus contributing to re-establish lost functions at the brain parenchyma–CSF interphase.Electronic supplementary materialThe online version of this article (doi:10.1007/s00401-012-0992-6) contains supplementary material, which is available to authorized users.
Highlights
Congenital hydrocephalus is a developmental brain disorder
The ependyma and the astrocyte layers share transport properties: (1) high expression of aquaporin 4, caveolin-1 and the endosome marker EEA1; (2) internalization into endocytic vesicles and early endosomes of Horseradish peroxidase (HRP) injected into the ventricle; (3) and a similar paracellular route of molecules moving between cerebrospinal fluid (CSF), the subependymal neuropile and the pericapillary space, as shown by lanthanum nitrate and HRP
We suggest that in foetalonset hydrocephalus, the astrocyte assembly at the denuded ventricular walls functions as a CSF–brain barrier involved in water and solute transport, contributing to reestablish lost functions at the brain parenchyma–CSF interphase
Summary
Congenital hydrocephalus is a developmental brain disorder. In the humans, its incidence is approximately 1–3 in every 1,000 live births. Dilatation of the brain ventricles and elevation of intraventricular pressure in rats with congenital or acquired hydrocephalus have harmful effects on the parenchyma and lead to oedema, oxidative stress [57], proteolytic damages in the white matter [15], cell death and reactive changes in glial cells [17]. Some of these alterations have been reported in human chronic hydrocephalus [16]. The astrocyte reaction that occurs in the brain of hydrocephalic animals has been thought to be a harmful phenomenon, leading some authors to test the effects of anti-inflammatory drugs in rats that have been made hydrocephalic postnatally [35, 36]
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