Affiliations: [a] Department of Neuroscience, Section of Experimental Traumatology, Karolinska Institutet, Stockholm, Sweden
| [b] Department of Clinical Science and Education, Södersjukhuset, Stockholm, Sweden
| [c] Department of Neuroscience, Section of Neurosurgery, Uppsala University, Uppsala, Sweden
Correspondence:
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Corresponding author: Dr. Mattias K. Sköld, M.D., Ph.D., Department of Neuroscience, Section of Experimental Traumatology, Karolinska Institutet, SE-171 77 Stockholm, Sweden. Tel.: +46 709 386971; E-mail: mattias.skold@ki.se.
Abstract: Background:In a model of injured spinal motor neurons where the avulsed spinal nerve is surgically reimplanted, useful regrowth of the injured nerve follows, both in animal experiments and clinical cases. This has led to surgical reimplantation strategies with subsequent partial functional motoric recovery. Still, the ideal time point for successful regeneration after reimplantation and the specific genetic profile of this time point is not known. Objective:To explore the temporal gene expression of the whole genome in the ventral spinal cord after reimplantation at different time points after avulsion. Methods:Totally 18 adult rats were subjected to avulsion of the left L5 root only (N = 3), avulsion followed by acute spinal reimplantation (N = 3), avulsion followed by 24 h (N = 3) or 48 h (N = 3) delayed reimplantation. Animals were allowed to survive 24 h after their respective surgery whereafter the ventral quadrant of the spinal cord at the operated side was harvested, processed for and analysed with Affymetrix Rat Gene ST 1.0 array followed by statistical analysis of gene expression patterns Results:Specific gene expression patterns were found at different time points after avulsion and reimplantation. Over all, early reimplantation seemed to diminish inflammatory response and support gene regulation related to neuronal activity compared to avulsion only or delayed reimplantation. In addition did gene activity after avulsion-reimplantation correspond to regeneration-associated genes typical for regeneration in the peripheral nervous system. Conclusions:Our study reveal that genetic profiling after this kind of injury is possible, that specific and distinct expression patterns can be found with early reimplantation being favourable over late and that regenerative activity in this kind of injury bears hallmark typical for peripheral nerve regeneration. These findings can be useful in elucidating specific genetic expression typical for successful nerve regeneration, hopefully not only in this specific model but in the nervous system in general.
