Astrocytes secrete basal lamina after hemisection of rat spinal cord

doi:10.1016/0006-8993(85)91507-0

Brain Research

Volume 327, Issues 1–2, 18 February 1985, Pages 135-141

https://doi.org/10.1016/0006-8993(85)91507-0 Get rights and content

Abstract

Basal lamina is reconstructed over the lesioned surface of the spinal cord. The following experiment (90 rats) studies the ultrastructure of the formation of this membrane and the immunohistochemistry of laminin production (a major secreted component of basal lamina). After hemisection of the spinal cord at T6 animals were prepared for electron microscopy or antilaminin-biotin-avidin-peroxidase incubation. Three-5 days posthemisection, antilaminin reaction product was observed in astrocytes and their processes which faced the lesion, endothelia of blood vessels or pia. Ultrastructurally (3 days), basal lamina was polymerizing as small projections on the surface of astrocytic membranes facing the lesion, endothelia or pia. By 5 days the basal lamina was a single membrane, folded multiple sheets or in swirls. At 6–10 days the antilaminin reaction and the basal lamina (except for duplications) did not differ from normal. Reactive astrocytes secrete laminin for at least 3–5 days after hemisection and form basal lamina on the lesioned surface of the spinal cord after spinal cord hemisection.

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Pre-existing astrocytes together with other cell types including pericytes (Table 1), that are located in the outer layer of the spinal cord, react to the injury and knit together an additional layer of cells that are apparently a strong barrier to surrounding influences. The newly formed tissue at the lesion site, namely the glial scar, functions as a molecular and physical barrier and blocks the further sprouting of axons from the pre-existing neurons and contributes to a failure in spinal cord regeneration (Barrett et al., 1981; Bernstein et al., 1985; Meletis et al., 2008; Barnabé-Heider et al., 2010). This suggests that the change in glial cell make up contributes to changes in the injury response and the architecture of the lesion site.
Repairing injured tissues / organs is one of the major challenges for the maintenance of proper organ function in adulthood. In mammals, the central nervous system including the spinal cord, once established during embryonic development, has very limited capacity to regenerate. In contrast, salamanders such as axolotls can fully regenerate the injured spinal cord, making this a very powerful vertebrate model system for studying this process. Here we discuss the cellular and molecular requirements for spinal cord regeneration in the axolotl. The recent development of tools to test molecular function, including CRISPR-mediated gene editing, has lead to the identification of key players involved in the cell response to injury that ultimately leads to outgrowth of neural stem cells that are competent to replay the process of spinal cord development to replace the damaged/missing tissue.
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Although this mechanism is still being defined, the integrin-laminin interaction is known to trigger PI3-kinase activation, Akt signaling, and cytoskeletal rearrangements favoring axon growth, suggesting that trophic factors and growth-promoting ECM molecules may converge on common intracellular signaling pathways to induce axon outgrowth (Chen et al., 2007). Some evidence suggests that, like Schwann cells, astrocytes may upregulate growth-promoting ECM components such as fibronectin and laminin after injury (Zamanian et al., 2012; Liesi et al., 1983; Bernstein et al., 1985). However, these modest proregenerative changes to the CNS ECM substrate are overshadowed by astrocyte upregulation of chondroitin sulfate proteoglycans (CSPGs), a family of ECM molecules highly inhibitory to axon outgrowth.
Enabling axon regeneration after central nervous system (CNS) injury remains a major challenge in neurobiology. One of the major differences between the injured peripheral nervous system (PNS) and CNS is the pro- and antiregenerative responses of their glial cell populations. In addition to intrinsic qualities of the neurons themselves, glial-driven changes to the neural environment have a significant impact on regenerative outcome. This Review presents a comparison of the glial response to injury between the CNS and PNS and highlights features of the PNS glial response that, with continued study, might reveal long-sought-after keys to achieving CNS repair.
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Microvessel integrity depends upon the interactions of astrocyte end-feet with the endothelium: both are required for the formation of the basal lamina matrix, and for the formation of the endothelial permeability barrier (“blood–brain barrier”) (Risau et al., 1986). Within capillaries, astrocytes and endothelial cells interact to form the intervening basal lamina barrier and the inter-endothelial tight junctions that constitute the permeability barrier (Bernstein et al., 1985; Webersinke et al., 1992; Nagano et al., 1993; Furuse et al., 1993, 1994, 1999; Itoh et al., 1993). Elegant xenograft experiments have demonstrated that the permeability barrier phenotype can be transplanted, and that its integrity requires the close interaction of endothelial cells with astrocyte end-feet (Hurwitz et al., 1993).
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Spinal cord and brain injuries lead to complex cellular and molecular interactions within the central nervous system in an attempt to repair the initial tissue damage. Many studies have illustrated the importance of the glial cell response to injury, and the influences of inflammation and wound healing processes on the overall morbidity and permanent disability that result. The abortive attempts of neuronal regeneration after spinal cord injury are influenced by inflammatory cell activation, reactive astrogliosis and the production of both growth promoting and inhibitory extracellular molecules. Despite the historical perspective that the glial scar was a mechanical barrier to regeneration, inhibitory molecules in the forming scar and methods to overcome them have suggested molecular modification strategies to allow neuronal growth and functional regeneration. Unlike myelin associated inhibitory molecules, which remain at largely static levels before and after central nervous system trauma, inhibitory extracellular matrix molecules are dramatically upregulated during the inflammatory stages after injury providing a window of opportunity for the delivery of candidate therapeutic interventions. While high dose methylprednisolone steroid therapy alone has not proved to be the solution to this difficult clinical problem, other strategies for modulating inflammation and changing the make up of inhibitory molecules in the extracellular matrix are providing robust evidence that rehabilitation after spinal cord and brain injury has the potential to significantly change the outcome for what was once thought to be permanent disability.
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Injury to the central nervous system (CNS) in adult mammals leads to significant pathology associated with permanent disability. The reactivity of glial cells to injuries in the brain and spinal cord, including the importance of inflammatory influences, has been identified as one component of the failure of the nervous system to regenerate when healing occurs. This chapter will review selected aspects of reactive gliosis at the tissue, cellular, and molecular levels as it relates to oligodendrocyte, astrocyte, and microglial/macrophage responses to trauma and the abortive attempts of neuronal regeneration. The historical perspective and modern approaches detailed in this review will demonstrate that the field of glial cell biology has allowed us to go beyond purely mechanical considerations of the glial scar, and in doing so has provided new insights into the complex reactions and interactions of glial cells following injury that generate the generally nonpermissive nature of lesion sites in the adult CNS. Recent advances in the field have demonstrated that significant regeneration can occur when modifications to the inflammatory sequelae are made to create optimal conditions for axon growth.
Glial Cells, Inflammation, and CNS Trauma: Modulation of the Inflammatory Environment After Injury Can Lead to Long-Distance Regeneration Beyond the Glial Scar
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Injury to the central nervous system (CNS) in adult mammals leads to significant pathology associated with permanent disability. The reactivity of glial cells to injuries in the brain and spinal cord, including the importance of inflammatory influences, has been identified as one component of the failure of the nervous system to regenerate when healing occurs. This chapter will review selected aspects of reactive gliosis at the tissue, cellular, and molecular levels as it relates to oligodendrocyte, astrocyte, and microglial/macrophage responses to trauma and the abortive attempts of neuronal regeneration. The historical perspective and modern approaches detailed in this review will demonstrate that the field of glial cell biology has allowed us to go beyond purely mechanical considerations of the glial scar, and in doing so has provided new insights into the complex reactions and interactions of glial cells following injury that generate the generally nonpermissive nature of lesion sites in the adult CNS. Recent advances in the field have demonstrated that significant regeneration can occur when modifications to the inflammatory sequelae are made to create optimal conditions for axon growth.

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Astrocytes secrete basal lamina after hemisection of rat spinal cord

Abstract

Exp. Neurol.

Brain Research

Exp. Neurol.

Brain Research

Int. Rev. Neurobiol.

Ensheathment and myelination of regenerating PNS fibers by transplanting optic nerve glia

Neurosci. Lett.

Greenfield's Neuropathology

Role of basal lamina in tissue interactions

Renal Physiol.

Possible functions of mesenchyme cell-derived fibronectin during formation of basal lamina

Synapse replacement in the nervous system of adult vertebrates

Physiol. Rev.

Basal lamina formation at the site of spinal cord transection

Ann. Neurol.

Basal lamina formation in thyroid epithelia in separated follicles in suspension culture

J. Cell Biol.