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Review
. 2021 Aug 25;10(9):2185.
doi: 10.3390/cells10092185.

Dorsal Root Injury-A Model for Exploring Pathophysiology and Therapeutic Strategies in Spinal Cord Injury

Håkan Aldskogius  1 , Elena N Kozlova  1
Affiliations
Review

Dorsal Root Injury-A Model for Exploring Pathophysiology and Therapeutic Strategies in Spinal Cord Injury

Håkan Aldskogius et al. Cells. .

Abstract

Unraveling the cellular and molecular mechanisms of spinal cord injury is fundamental for our possibility to develop successful therapeutic approaches. These approaches need to address the issues of the emergence of a non-permissive environment for axonal growth in the spinal cord, in combination with a failure of injured neurons to mount an effective regeneration program. Experimental in vivo models are of critical importance for exploring the potential clinical relevance of mechanistic findings and therapeutic innovations. However, the highly complex organization of the spinal cord, comprising multiple types of neurons, which form local neural networks, as well as short and long-ranging ascending or descending pathways, complicates detailed dissection of mechanistic processes, as well as identification/verification of therapeutic targets. Inducing different types of dorsal root injury at specific proximo-distal locations provide opportunities to distinguish key components underlying spinal cord regeneration failure. Crushing or cutting the dorsal root allows detailed analysis of the regeneration program of the sensory neurons, as well as of the glial response at the dorsal root-spinal cord interface without direct trauma to the spinal cord. At the same time, a lesion at this interface creates a localized injury of the spinal cord itself, but with an initial neuronal injury affecting only the axons of dorsal root ganglion neurons, and still a glial cell response closely resembling the one seen after direct spinal cord injury. In this review, we provide examples of previous research on dorsal root injury models and how these models can help future exploration of mechanisms and potential therapies for spinal cord injury repair.

Keywords: astrocyte; gene regulation; microglia; nerve degeneration; nerve regeneration; sensory neuron; transplantation; trophic factor.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Intact, the lumbar dorsal root of the adult rat. Horizontal section through several dorsal rootlets, immunostained with antibodies to laminin (green) and glial fibrillary acidic protein (GFAP; red). The dorsal root transitional zone is formed by cone-shaped peripheral projections of central nervous tissue, so-called central tissue projections (CTP; red), which interdigitate with the peripheral nervous compartment of the root (green). ×200. Reproduced with permission from Aldskogius, H., Kozlova, E.N., Brain Research Reviews; published by Elsevier, 2002 [35].
Figure 2
Figure 2
Lumbar dorsal roots following ipsilateral dorsal root injury. Horizontal sections, immunostained with antibodies to laminin (green) and GFAP (red). The extensive outgrowth of astroglial processes (red and yellow) into the peripheral compartment is shown at one week (above) and two weeks (below) following injury. ×200. Reproduced with permission from Aldskogius, H., Kozlova, E.N., Brain Research Reviews; published by Elsevier, 2002 [35].
Figure 3
Figure 3
Scheme of experiment with human embryonic/fetal dorsal root ganglion (DRG) transplant (T) in the cavity of the extirpated native DRG of an adult rat recipient. Sensory axons from the transplant grow through the host DREZ and make synaptic contacts in the host spinal cord. For further information. Reproduced with permission from Kozlova, E.N., Seiger, A., Aldskogius, H., Journal of Neurocytology; published by Springer, 1997 [152,153].
Figure 4
Figure 4
Two options based on the use of stem cell-based transplants at the DREZ, to facilitate entry of injured dorsal root axons (left) or to create a neuronal relay between dorsal root axons (forming synapses with the relay) and the host spinal cord circuitry (right).
Figure 5
Figure 5
Principle scheme to use the DREZ as an entry point for axons growing in a bridge circumventing a spinal cord injury. (A) Axons from injured descending pathways (S) grow into and within a peripheral nerve graft (or biomimetic conduit) and may be able to enter the spinal cord through the intact or drug/cell modified DREZ. (B) Axons from an intraspinal transplant (T) grow through the bridge and may, because of their immaturity, be able to grow through the intact or reactive DREZ.
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