Abstract
Nerve axonal injury and associated cellular mechanisms leading to peripheral nerve damage are important topics of research necessary for reducing disability and enhancing quality of life. Model systems that mimic the biological changes that occur during human nerve injury are crucial for the identification of cellular responses, screening of novel therapeutic molecules, and design of neural regeneration strategies. In addition to in vivo and mathematical models, in vitro axonal injury models provide a simple, robust, and reductionist platform to partially understand nerve injury pathogenesis and regeneration. In recent years, there have been several advances related to in vitro techniques that focus on the utilization of custom-fabricated cell culture chambers, microfluidic chamber systems, and injury techniques such as laser ablation and axonal stretching. These developments seem to reflect a gradual and natural progression towards understanding molecular and signaling events at an individual axon and neuronal-soma level. In this review, we attempt to categorize and discuss various in vitro models of injury relevant to the peripheral nervous system and highlight their strengths, weaknesses, and opportunities. Such models will help to recreate the post-injury microenvironment and aid in the development of therapeutic strategies that can accelerate nerve repair.
Highlights
Mammalian axons in the peripheral nervous system (PNS), unlike their counterparts in the central nervous system (CNS), possess the ability to repair and regenerate to a large extent [1]
This study found that within 6 h of impact, almost all dorsal root ganglion (DRG) neurons demonstrated cytoskeletal disruption, plasma membrane dysfunction, and neurofilament tangles [166]. In another blast injury model that was closer to reality, PC-12 cells submerged in water were subjected to the effect of single and multiple primary blasts generated from research department explosives (RDX)
Peripheral nerve injuries (PNI) coupled with poor nerve regeneration capabilities can be debilitating and compromises overall quality of life
Summary
Mammalian axons in the peripheral nervous system (PNS), unlike their counterparts in the central nervous system (CNS), possess the ability to repair and regenerate to a large extent [1]. Newer strategies that are more practical and cost-effective in managing nerve injuries are much needed. The development of such innovative treatment options requires a thorough understanding of the cellular and molecular mechanisms involved in peripheral nerve repair and healing. Isolated cellular systems and animal models have proven to be extremely useful in understanding PNI-associated molecular mechanisms, electrophysiological alterations [13,14] and changes in gene expression. Amongst the various experimental strategies to address PNI, well-designed in vitro models, in particular, have been crucial in deciphering, discovering, and identifying many of the molecular determinants and events of nerve repair [17]. For in vivo and mathematical models of axonal injury, readers are directed towards other excellent reviews [7,18,19] for a better understanding of their use and application
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