The astrocyte/meningeal cell interface – a barrier to successful nerve regeneration?

Abstract

Following injuries to the adult mammalian CNS meningeal cells migrate into the lesion cavity, forming a fibrotic scar and accessory glia limitans. This infiltration re-establishes the meningeal layer that normally surrounds the CNS, and so reforms the barrier between the CNS and external environment, thus protecting the damaged region from events outside it. However, the newly formed meningeal layer and glia limitans may impede subsequent nerve regeneration through the injured region. This structure can be modelled in vitro using an astrocyte/meningeal co-culture system. We have examined patterns of neurite outgrowth on such cultures, and we find that axons cross readily from meningeal cells to astrocytes, but are unwilling to cross in the other direction. The distribution of cell surface and matrix molecules on these cultures is described, and the effect of various pharmacological interventions which can affect axon growth between the two cell types is summarised in this review.

Nano neuro knitting: Peptide nanofiber scaffold for brain repair and axon regeneration with functional return of vision

“…These obstacles are: (i) scar tissue formation after tissue injury (1-7); (ii) gaps in nervous tissue formed during phagocytosis of dying cells after injury (3,(8)(9)(10)(11)(12)(13)(14); (iii) factors that inhibit axon growth in the mature mammalian CNS (1,3,(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20); and (iv) failure of many adult neurons to initiate axonal extension (3, 8-12, 15, 17, 21, 22). In this paper, we describe the creation of a permissive environment for axonal regrowth using a synthetic biological nanomaterial that self assembles in vivo, with components that break down into beneficial building blocks and produce no adverse effects on the CNS.…”

Perivascular Fibroblasts Form the Fibrotic Scar after Contusive Spinal Cord Injury

“…However, much less is known about the fibrotic scar, which is typically characterized by excess deposition of extracellular matrix molecules. Most of our current knowledge comes from in vitro coculture assays of primary astrocytes and meningeal fibroblasts that mimic the astrocyte-fibroblast border that forms after SCI in vivo (Rudge and Silver, 1990;Shearer and Fawcett, 2001). When neurons are placed on top of this coculture, they prefer to grow over astrocytes and avoid fibroblasts, indicating that fibroblasts are less permissive or inhibitory to axon growth.…”

Les molécules qui dirigent la migration des astrocytes

“…Cette cicatrice constitue une nouvelle barrière imperméable entre le système nerveux et les tissus détériorés, permettant ainsi le rétablissement de conditions propices à la régénération neuronale au sein du système nerveux. Cependant, les nouveaux axones ne peuvent pas se développer au-delà de la cicatrice, ce qui limite spatialement les capacités de régénération [3]. L'orientation et la migration des astrocytes, qui contribuent à déterminer la position de la cicatrice gliale, jouent donc un rôle essentiel dans les capacités de récupé-ration du système nerveux après une lésion accidentelle ou pathologique.…”

“…Des études ont montré que la rayure d'une monocouche astrocytaire en culture provoque une réorientation des cellules et une migration similaires à celles observées in vivo à la suite d'une lésion [3,5]. Nous avons utilisé ce modèle in vitro pour caractériser la réponse astrocytaire et en particulier les mécanismes qui contrôlent la réorientation et la migration de ces cellules [6].…”