Introduction: Post-traumatic syringomyelia produces a significant burden of pain and neurological deficits for patients with spinal cord injury. The mechanism of syrinx formation is unknown and treatment is often ineffective. Previous studies have demonstrated that fluid flow enters syrinxes from the subarachnoid space via perivascular spaces, however other pathways may be involved. It has been proposed that a damaged blood-spinal cord barrier (BSCB) provides another pathway for fluid to enter syrinxes. The purpose of this study was to investigate whether or not the integrity of the BSCB is compromised in an animal model of post-traumatic syringomyelia, and if so, whether this deficiency plays a role in the induction or subsequent enlargement of a syrinx.

Methods: The excitotoxic amino acid and arachnoiditis model of syringomyelia was used to study the structural and functional integrity of the BSCB in 27 Sprague-Dawley rats. In this model, quisqualic acid is injected into the cord to create an initial cyst. The addition of subarachnoid kaolin to create arachnoiditis results in a reliable model of syringomyelia [1]. Structural integrity of the blood-spinal cord barrier was assessed using immunoreactivity to endothelial barrier antigen (EBA) and loss of functional integrity was assessed by extravasation of intravascular horseradish peroxidise (HRP). Animals were studied at 3 days, or 1, 3, 6, or 12 weeks after surgery. There were laminectomy-only and saline injection controls at each time point.

Results: Syrinxes formed in 15 of 17 animals injected with excitotoxic amino acid. There was loss of structural and functional integrity of the BSCB in the syrinx animals at all time points. There was wide-spread disruption of the barrier at early time points, followed by recovery of the barrier except for vessels immediately adjacent to the syrinx.

Discussion: This study has demonstrated a prolonged structural and functional disruption of the BSCB. Loss of functional integrity of the barrier, with fluid entering the interstitial space of the spinal cord, may contribute to initial cyst formation after spinal cord injury and subsequent enlargement of the cyst to form post-traumatic syringomyelia.

Introduction Approximately one quarter of spinal cord injury patients will develop post-traumatic syringomyelia. This condition can produce devastating neurological deficits, and treatment is often not successful. The pathogenesis is unknown, however it is likely that initial cyst formation plays an important role in subsequent syrinx development. An up-regulated inflammatory process observed following contusive and transective spinal cord injury has been proposed as a contributory factor in secondary spinal cord damage. Specifically, a depletion or suppression of macrophages following injury is shown to preserve neurons and myelinated axons. This study examines the role of inflammation following excitotoxic spinal cord injury, a potent precursor to syrinx formation.

Methods Twenty-four male Sprague-Dawley rats were divided into six groups. Twenty rats received four 0.5 μL injections of 24 mg/ mL quisqualic acid and 1% Evans blue from the rostral C8 to the caudal T1 level. Ten microlitres of 250 mg/ mL kaolin were then injected into the subarachnoid space. Animals were sacrificed at 1, 5, 10, 20 or 50 days following the injections. There were four normal control animals. Spinal cord tissue was frozen and sectioned, and cytoplasmic antigen ED1 was detected immunohistochemically with anti-ED1 antibody. This antibody is specific to phagocytic macrophages and reactive microglia. The area and density of ED1 was semi-quantitated.

Results Few ED1 positive cells were observed in normal controls in the subarachnoid space (SAS) and cord vessels. Day 1 animals displayed ED1 positive cells within 50% of the subarachnoid space. ED1 positive cells within cord vessels were also slightly increased (10%). Day 5 animals showed strong staining through 50% of grey matter, predominantly on the side of injury. This was also observed in cord above and below the level of Quisqualic Acid injection. Arachnoiditis was observed by day 10 combined with strong staining through grey and white matter. ED1 positive staining area was again increased by day 20, comprising 70% grey matter on the injured and non-injured sides of the cord, which was limited to the level Quisqualic Acid injection. By day 50 moderate staining was observed in the SAS and white matter.

Discussion Cytoplasmic antigen ED1 cells were observed, reaching a peak at 20 days following excito-toxic spinal cord injury. Phagocytic macrophage proliferation might play a role in secondary spinal cord damage and initial cyst formation. The role of macrophages and the release of their inflammatory cytokines, reactive nitrogen and oxygen intermediates require further examination.

Introduction: It has been suggested that arachnoiditis predisposes to post-traumatic syringomyelia formation by obstructing subarachnoid cerebrospinal fluid flow and enhancing perivascular flow into the cord. In an animal model of post-traumatic syringomyelia (PTS), fluid flow in spinal cord perivascular spaces (PVS) is greater at the level of arachnoiditis and syrinx than at other levels and fluid enters the syrinx via the PVS. This study was performed to determine the effects of cerebrospinal fluid (CSF) diversion from the subarachnoid space on perivascular flow and syrinx formation in PTS.

Methods: Twenty six male Sprague-Dawley rats were investigated using the CSF tracer horseradish peroxidase (HRP), the excitotoxic and arachnoiditis model of PTS, and lumboperitoneal shunt insertion. Four experimental groups consisted of syrinx only and shunt only controls, and shunt insertion before or after syrinx formation. CSF flow studies were performed 6 weeks following the final intervention. Grading scales were used to quantify HRP staining.

Results: Syrinxes formed in all animals. Perivascular flow was greatest at the level of the syrinx. Cerebral cortex perivascular flow was significantly reduced following shunt insertion in animals with a syrinx (p< 0.05). Shunt insertion did not alter syrinx length or size, but did reduce the number of animals with evidence of sensory disturbances. There were no significant differences between shunt and syrinx first groups.

Discussion: Increasing distal subarachnoid space compliance does not affect local CSF flow into the spinal cord and syrinx. These results suggest that localised alterations in compliance, as opposed to obstruction from traumatic arachnoiditis, act as an important factor in syrinx pathogenesis.

INTRODUCTION: Apoptosis has been observed following experimental contusive and transective spinal cord injury, but it is not known whether this is related to secondary excitotoxic injury or other factors. This study examines apoptosis after a purely excitotoxic injury and the relationship between apoptosis and syrinx formation.

METHODS: Twenty-four male Sprague-Dawley rats were divided into six groups. Twenty rats received four 0.5 μL injections of 24 mg/mL quisqualic acid and 1% Evans blue between the rostral C8 and caudal T1 level. Ten microliters of 250 mg/mL kaolin were then injected into the subarachnoid space. Animals were sacrificed at 1, 5, 10, 20 and 50 days following the injections. There were four control animals. Spinal cord tissue was frozen and sectioned, and damaged DNA was detected immunohistochemically by using anti-single-stranded DNA monoclonal antibody. The area and density of single strand DNA were semi-quantitated.

RESULTS: No significantly damaged DNA was found in the 1 day group. Light staining of single-stranded DNA was observed at C6, C7, T1 and T2 levels in 30% of the section area in the 5 and 10 day groups. Moderate staining of damaged DNA occurred at C7 and T1 levels in 25–30% of the section area at 20 day group. Syrinxes formed in this group. Heavy staining and larger syrinxes were noted in the 50 day group.

DISCUSSION: Apoptosis increased with time after excitotoxic injury. These findings suggest that apoptosis may play a pivotal role in syrinx pathogenesis.

INTRODUCTION: It has been suggested that arachnoiditis predisposes to post-traumatic syringomyelia formation by obstructing subarachnoid cerebrospinal fluid flow and enhancing perivascular flow into the cord. In an animal model of post-traumatic syringomyelia (PTS), fluid flow in spinal cord perivascular spaces (PVS) is greater at the level of arachnoiditis and syrinx than at other levels and fluid enters the syrinx via the PVS. This study was performed to determine the effects of cere-brospinal fluid (CSF) diversion from the subarachnoid space on perivascular flow and syrinx formation in PTS.

METHODS: Twenty six male Sprague-Dawley rats were investigated using the CSF tracer horseradish peroxidase (HRP), the excitotoxic and arachnoiditis model of PTS, and lumboperitoneal shunt insertion. Four experimental groups consisted of syrinx only and shunt only controls, and shunt insertion before or after syrinx formation. CSF flow studies were performed six weeks following the final intervention. Grading scales were used to quantify HRP staining.

RESULTS: Syrinxes formed in all animals. Perivascular flow was greatest at the level of the syrinx. Cerebral cortex perivascular flow was significantly reduced following shunt insertion in animals with a syrinx (p< 0.05). Shunt insertion did not alter syrinx length or size, but did reduce the number of animals with evidence of sensory disturbances. There were no significant differences between shunt and syrinx first groups.

DISCUSSION: Increasing distal subarachnoid space compliance does not affect local CSF flow into the spinal cord and syrinx. These results suggest that localised alterations in compliance, as opposed to obstruction from traumatic arachnoiditis, act as an important factor in syrinx pathogenesis.