The Role of Excitotoxic Injury in Post-Traumatic Syringomyelia

Abstract

Fifty percent of patients with neurological deterioration from post-traumatic syringomyelia do not respond to treatment. Treatment failure is due in part to an incomplete understanding of the underlying aetiology. An animal model that mimics the human disease is required to investigate underlying pathophysiology and treatment options. A previous study was designed to mimic trauma-induced effects on the spinal cord that result in syringomyelia, combining an excitotoxic insult with kaolin-induced arachnoiditis. In this excitotoxic model, syringes were produced in 82% of animals. The aims of the current study were to improve the model to produce syringes in all animals treated, to examine the relative influences of excitotoxic injury and neuronal loss on syrinx formation, and to use magnetic resonance imaging (MRI) to examine syringes non-invasively. A temporal and dose profile of intraparenchymal quisqualic acid (QA) and subarachnoid kaolin was performed in Sprague Dawley rats. MRI was used to study four syrinx and six control animals. In one subgroup of animals surviving for 6 weeks, 100% (eight of eight) developed syringes. Syrinx formation and enlargement occurred in a dose and time dependent manner, whilst significant neuronal loss was only dose dependent. Animal syrinx histology closely resembled human post-traumatic syringomyelia. Axial T2-weighted MR images demonstrated syrinx presence. The results suggest that the formation of an initial cyst predisposes to syrinx formation in the presence of subarachnoid adhesions.

Reaction of endogenous progenitor cells in a rat model of posttraumatic syringomyelia

“…Rats in the intact group did not undergo surgery, the sham-operated group underwent laminectomies only, and the syrinx group underwent a syrinx induction procedure as described previously. 5,49 Briefly, after a C-7 and T-1 laminectomy, 0.5 ml of 24 mg/ ml quisqualic acid (Tocris Bioscience) was injected into the spinal cord at the C-8 level to mimic an excitotoxic injury with initial cyst, and then 10 ml of 250 mg/ml kaolin (Sigma-Aldrich) in saline was injected into the subarachnoid space at the C-8 level to create arachnoiditis. This model has been shown to result in expanding syringes in the majority of experimental animals.…”

“…This model has been shown to result in expanding syringes in the majority of experimental animals. 5 …”

“…5 Briefly, 7-mm paraffin cross-sections of spinal cord were dewaxed using xylene and an alcohol series. Slides were placed in hematoxylin for 5 minutes, followed by a dip in 2% acid alcohol and then in lithium carbonate.…”

“…20,26,28,45 In this model, an excitatory amino acid triggers inflammation, cellular injury, and neuronal death and contributes to the initial cyst formation. 5,49 A subsequent imbalance between CSF inflow and outflow causes syrinx enlargement. 6,[37][38][39][40] It is unclear when cyst formation finishes and at what time its enlargement begins, although the 2 stages probably overlap.…”

Longitudinal measurements of syrinx size in a rat model of posttraumatic syringomyelia

“…1,10,11,15,19,22 In animal studies, posttraumatic syringomyelia has traditionally been assessed using histological methods. [7][8][9]16 These studies have been extremely valuable in adding to our knowledge of the condition; however, histology offers only a snapshot of a syrinx cavity. It does not allow the progression and expansion of the syrinx to be visualized.…”