Abstract

Dorsal root injury is a situation not expected to be followed by a strong regenerative growth, or growth of the injured axon into the central nervous system of the spinal cord, if the central axon of the dorsal root is injured but of strong regeneration if subjected to injury to the peripherally projecting axons. The clinical consequence of axonal injury is loss of sensation and may also lead to neuropathic pain. In this study, we have used in situ hybridization to examine the distribution of mRNAs for the neural guidance molecules semaphorin 3A (SEMA3A), semaphorin 3F (SEMA3F), and semaphorin 4F (SEMA4F), their receptors neuropilin 1 (NP1) and neuropilin 2 (NP2) but also for the neuropilin ligand vascular endothelial growth factor (VEGF) and Tenascin J1, an extracellular matrix molecule involved in axonal guidance, in rat dorsal root ganglia (DRG) after a unilateral dorsal rhizotomy (DRT) or sciatic nerve transcetion (SNT). The studied survival times were 1–365 days. The different forms of mRNAs were unevenly distributed between the different size classes of sensory nerve cells. The results show that mRNA for SEMA3A was diminished after trauma to the sensory nerve roots in rats. The SEMA3A receptor NP1, and SEMA3F receptor NP2, was significantly upregulated in the DRG neurons after DRT and SNT. SEMA4F was upregulated after a SNT. The expression of mRNA for VEGF in DRG neurons after DRT showed a significant upregulation that was high even a year after the injuries. These data suggest a role for the semaphorins, neuropilins, VEGF, and J1 in the reactions after dorsal root lesions.

Highlights

  • Primary sensory neurons represent a link between the peripheral nervous system (PNS) and the central nervous system (CNS)

  • It may be argued that the measurements are not independent, these recorded values from individual neurons were analyzed using one-way ANOVA Kruskal–Wallis statistics (Dunn’s Multiple Comparison Test), which indicated that semaphorin 3A (SEMA3A) mRNA was significantly down regulated in the dorsal root ganglia (DRG) (P < 0.001) 3, 7, and 21 days after the dorsal root injury

  • Examination of sections from rats subjected to sciatic nerve transection (SNT) or Sciatic Nerve Crush (SNC) showed that the labeling signal for SEMA3A in the DRG was largely unaltered after these injuries

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Summary

Introduction

Primary sensory neurons represent a link between the peripheral nervous system (PNS) and the central nervous system (CNS). Axon regrowth is possible in the PNS environment of the dorsal root, but the sprouts are typically arrested at the PNS–CNS border [3], and replantation of avulsed dorsal roots has not been considered to be useful even if recent studies have indicated that this situation can be changed by pharmacological intervention [4] or special procedures, such as removal of the DRG [5, 6] Due to this difference in response to injury, the DRG neurons offer the possibility to study the same neuron after two different kinds of injury where on is followed by regeneration (the peripheral injury) but the other one (central injury) followed by much less regenerative capacity

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