The Extracellular Environment of the CNS: Influence on Plasticity, Sprouting, and Axonal Regeneration after Spinal Cord Injury

Abstract

The extracellular environment of the central nervous system (CNS) becomes highly structured and organized as the nervous system matures. The extracellular space of the CNS along with its subdomains plays a crucial role in the function and stability of the CNS. In this review, we have focused on two components of the neuronal extracellular environment, which are important in regulating CNS plasticity including the extracellular matrix (ECM) and myelin. The ECM consists of chondroitin sulfate proteoglycans (CSPGs) and tenascins, which are organized into unique structures called perineuronal nets (PNNs). PNNs associate with the neuronal cell body and proximal dendrites of predominantly parvalbumin-positive interneurons, forming a robust lattice-like structure. These developmentally regulated structures are maintained in the adult CNS and enhance synaptic stability. After injury, however, CSPGs and tenascins contribute to the structure of the inhibitory glial scar, which actively prevents axonal regeneration. Myelin sheaths and mature adult oligodendrocytes, despite their important role in signal conduction in mature CNS axons, contribute to the inhibitory environment existing after injury. As such, unlike the peripheral nervous system, the CNS is unable to revert to a “developmental state” to aid neuronal repair. Modulation of these external factors, however, has been shown to promote growth, regeneration, and functional plasticity after injury. This review will highlight some of the factors that contribute to or prevent plasticity, sprouting, and axonal regeneration after spinal cord injury.

<p>Magnetic Field Promotes Migration of Schwann Cells with Chondroitinase ABC (ChABC)-Loaded Superparamagnetic Nanoparticles Across Astrocyte Boundary in vitro</p>

“…In previous studies, CSPGs were highly expressed in the site of spinal cord injury. 54,55 In the present study, we found that the fluorescence intensity of CS56 has been decreased after the supplementation of pure ChABC into the spinal cord section. In addition, the fluorescence intensity of CS56 of the spinal cord section was also decreased by the culture medium of PEI-SPIONs/ChABC/ SCs.…”

Dissecting the Dual Role of the Glial Scar and Scar-Forming Astrocytes in Spinal Cord Injury

“…Among these key inhibitory molecules, CSPGs are the most prominent. CSPGs, a proteoglycan family characterized by chondroitin sulfate side chains, are thought to be released predominantly from neurons and scar-forming astrocytes (Quraishe et al, 2018). It has long been thought that CSPGs are crucial inhibitory factors of CNS axonal regeneration, making them a primary cause of the inhibitory roles of the glial scar (McKeon et al, 1991).…”

The mouse olfactory peduncle 4: Development of synapses, perineuronal nets, and capillaries

“…Perineuronal nets around neurons regulate neuritic growth and synaptogenesis during early life. Maturation of these extracellular matrices restricts synaptic plasticity and stabilizes functional synapses (Bikbaev et al, 2015;Clarris et al, 2000;Lensjø et al, 2017;Quraishe et al, 2018;Sorg et al, 2016;Valenzuela et al, 2014;van 't Spijker & Kwok, 2017) and disrupting them can extend early sensitive periods (e.g., monocular deprivation in the cerebral cortex or thalamus; Lensjø et al, 2017) and allow synaptic potentiation of normally plasticityresistant neurons (Carstens, Phillip, Pozzo-Miller, Weinberg, & Dudek, 2016). Substantial regional differences in the expression of extracellular matrix proteins during development have been reported (Dauth et al, 2016;Sonntag, Blosa, Schmidt, Rübsamen, & Morawski, 2015).…”

“…These mesh-like extracellular structures envelop neuronal processes and regulate the number and types of synapses. Their maturation is associated with the end of early critical periods of synaptogenesis in several brain regions (Bikbaev, Frischknecht, & Heine, 2015;Clarris, Uwe Rauch, & Key, 2000;Lensjø, Lepperød, Dick, Hafting, & Fyhn, 2017;Quraishe, Forbes, & Andrews, 2018;Sorg et al, 2016;Valenzuela et al, 2014;van 't Spijker & Kwok, 2017). Finally, the rapid changes associated with growth in the structure necessitate substantial energy: a small study addressed this issue by examining age-related changes in vasculature.…”