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Review
. 2018;205(5-6):372-395.
doi: 10.1159/000494667. Epub 2018 Dec 5.

Biomaterial Approaches to Modulate Reactive Astroglial Response

Jonathan M Zuidema  1 , Ryan J Gilbert  2   3 , Manoj K Gottipati  4   5   6
Affiliations
Review

Biomaterial Approaches to Modulate Reactive Astroglial Response

Jonathan M Zuidema et al. Cells Tissues Organs. 2018.

Abstract

Over several decades, biomaterial scientists have developed materials to spur axonal regeneration and limit secondary injury and tested these materials within preclinical animal models. Rarely, though, are astrocytes examined comprehensively when biomaterials are placed into the injury site. Astrocytes support neuronal function in the central nervous system. Following an injury, astrocytes undergo reactive gliosis and create a glial scar. The astrocytic glial scar forms a dense barrier which restricts the extension of regenerating axons through the injury site. However, there are several beneficial effects of the glial scar, including helping to reform the blood-brain barrier, limiting the extent of secondary injury, and supporting the health of regenerating axons near the injury site. This review provides a brief introduction to the role of astrocytes in the spinal cord, discusses astrocyte phenotypic changes that occur following injury, and highlights studies that explored astrocyte changes in response to biomaterials tested within in vitro or in vivo environments. Overall, we suggest that in order to improve biomaterial designs for spinal cord injury applications, investigators should more thoroughly consider the astrocyte response to such designs.

Keywords: Astrocytes; Biomaterials; Reactive gliosis; Spinal cord injury.

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Conflict of interest statement

4.2. Statement of Ethics

The authors have no ethical conflicts to disclose.

4.3. Disclosure Statement

The authors have no conflicts of interest to declare.

Figures

Fig. 1.
Fig. 1.
Schematic showing the response of astrocytes to a spinal cord injury. NAIVE The top panel shows astrocytes and microglia spread throughout an uninjured spinal cord. The astrocytes are predominantly present in the white matter and are organized in non-overlapping domains. The inset on the right shows an individual astrocyte before injury. ACUTE The middle panel shows an enhanced image of the acute changes observed following a contusion spinal cord injury. There is an activation of microglia, infiltrating macrophages and astrocytes, all of which are recruited to the lesion site. The reactive astrocytes undergo hypertrophy and show an increase in intermediate filament expression, proliferation and neurotoxin release, changes presented in an enlarged inset on the right along with the associated text. There is also a significant axonal dieback and an accumulation of myelin debris. CHRONIC The bottom panel shows the chronic changes observed following a contusion spinal cord injury. The reactive astrocytes increase their production of proteoglycans and form a thick glial scar, as presented in the enlarged inset on the right with the text. The activated microglia and macrophages also persist within the lesion area.
Fig. 2.
Fig. 2.
Astrocyte morphologies imaged in vitro. Astrocytes demonstrate several morphologies in vitro depending on their culture environment. 1 On typical smooth, two-dimensional surfaces astrocytes demonstrate a flat, spread morphology. 2 Astrocytes cultured in three-dimensional hydrogels show many different morphologies, including stellate astrocytes that extend processes in all directions, bipolar astrocytes that extend two processes, round astrocytes with no processes, and perivascular astrocytes, that extend processes that resemble endfeet. 3 Astrocytes cultured on isotropic microtopographies predominately display stellate morphologies, with extension of several processes. 4 Astrocytes cultured on anisotropic micropatterns and microstructures display both bipolar and stellate morphologies that align along the direction of the surface they are cultured on. The many different morphologies suggest that astrocytes are impacted by their culture environment, and further study is needed to gain a full understanding of the astrocyte response to biomaterials.
See this image and copyright information in PMC

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References

    1. Agulhon C, Petravicz J, McMullen AB, Sweger EJ, Minton SK, Taves SR, Casper KB, Fiacco TA, McCarthy KD (2008) What Is the Role of Astrocyte Calcium in Neurophysiology? Neuron 59(6): 932–946. - PMC - PubMed
    1. Almad A, Sahinkaya FR, McTigue DM (2011) Oligodendrocyte fate after spinal cord injury. Neurotherapeutics 8(2): 262–273. - PMC - PubMed
    1. Amar AP, Larsen DW, Teitelbaum GP (2005) Percutaneous spinal interventions, pp 561–568. - PubMed
    1. Anderson CM, Swanson RA (2000) Astrocyte glutamate transport: Review of properties, regulation, and physiological functions. Glia 32(1): 1–14. - PubMed
    1. Anderson MA, Ao Y, Sofroniew MV (2014) Heterogeneity of reactive astrocytes, pp 23–29. - PMC - PubMed

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