Abstract

The central nervous system (CNS) does not recover from traumatic axonal injury, but the peripheral nervous system (PNS) does. We hypothesize that this fundamental difference in regenerative capacity may be based upon the absence of stimulatory mechanical forces in the CNS due to the protective rigidity of the vertebral column and skull. We developed a bioreactor to apply low-strain cyclic axonal stretch to adult rat dorsal root ganglia (DRG) connected to either the peripheral or central nerves in an explant model for inducing axonal growth. In response, larger diameter DRG neurons, mechanoreceptors and proprioceptors showed enhanced neurite outgrowth as well as increased Activating Transcription Factor 3 (ATF3).

Highlights

  • During the development of multicellular organisms, tissues form and grow under the presence of mechanical forces [1,2]

  • Using a custom-built bioreactor, we found a specific stretch amount that did not lead to further nerve damage but increased overall outgrowth in our central nervous system (CNS) located nerve-dorsal root ganglia (DRG) model

  • An oscillator (Figure 1E) controls the bioreactor sitting partially inside the incubator (Figure 1B), which is kept at a constant temperature, humidity, and CO2 levels

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Summary

Introduction

During the development of multicellular organisms, tissues form and grow under the presence of mechanical forces [1,2]. The nervous system is subjected to mechanical forces that guide its development, form its shape and act as cues for the perception of the internal physiology of the body (proprioception) or the outside world (mechano-sensation) [1,4,5]. The mature central nervous system (CNS) is enclosed in a stiff bony structure, either the skull or the vertebral column, providing protection as well as shape. The mature peripheral nervous system (PNS) is not enveloped by bone but rather intermingled with internal organs and tissues, more susceptible to mechanical cues. The PNS retains its ability to re-grow functional connections after a lesion

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