The Structural Response of the Human Head to a Vertex Impact.

In experimental models of cervical spine trauma caused by near-vertex head-first impact, a surrogate headform may be substituted for the cadaveric head. To inform headform design and to verify that such substitution is valid, the force-deformation response of the human head with boundary conditions relevant to cervical spine head-first impact models is required. There are currently no biomechanics data that characterize the force-deformation response of the isolated head supported at the occiput and compressed at the vertex by a flat impactor. The effect of impact velocity (1, 2 or 3 m/s) on the response of human heads (N = 22) subjected to vertex impacts, while supported by a rigid occipital mount, was investigated. 1 and 2 m/s impacts elicited force-deformation responses with two linear regions, while 3 m/s impacts resulted in a single linear region and skull base ring fractures. Peak force and stiffness increased from 1 to 2 and 3 m/s. Deformation at peak force and absorbed energy increased from 1 to 2 m/s, but decreased from 2 to 3 m/s. The data reported herein enhances the limited knowledge on the human head's response to a vertex impact, which may allow for validation of surrogate head models in this loading scenario.

Severity-dependent expression of pro-inflammatory cytokines in traumatic spinal cord injury in the rat.

The post-traumatic inflammatory response in acute spinal cord contusion injury was studied in the rat. Mild and severe spinal cord injury (SCI) was produced by dropping a 10 g weight from 3 and 12 cm at the T12 vertebral level. Increased immunoreactivity of TNF-alpha in mild and severe SCI was detected in neurons at 1 h post-injury, and in neurons and microglia at 6 h post-injury, with a less significant increase in mild SCI. Expression was short-lived and declined sharply by 1 d post-injury. RT-PCR showed an early significant up-regulation of IL-1 beta, IL-6 and TNF-alpha mRNAs, maximal at 6 h post-injury with return to control levels by 24 h post-injury, the changes being less statistically significantly in mild SCI. Western blot showed early transient increases of IL-1 beta, IL-6 and TNF-alpha proteins in severe SCI but not mild SCI. Immunocytochemical, western blotting and RT-PCR analyses suggest that endogenous cells (neurons and microglia) in the spinal cord, not blood-borne leucocytes, contribute to IL-1 beta, IL-6 and TNF-alpha production in the post-traumatic inflammatory response and that their up-regulation is greater in severe than mild SCI.

Early expression and cellular localization of proinflammatory cytokines interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in human traumatic spinal cord injury.

STUDY DESIGN: Post-traumatic inflammatory response was studied in 11 human cases of acute spinal cord contusion injury. OBJECTIVES: To examine the inflammatory cellular response and the immunocytochemical expression and localization of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in human spinal cord after contusion injury. SUMMARY OF BACKGROUND DATA: : The post-traumatic inflammatory response plays an important role in secondary injury mechanisms after spinal cord injury, and interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha are key inflammatory mediators. METHODS: : The study group comprised 11 patients with spinal cord contusion injury and 2 normal individuals. Histologic and immunocytochemical assessments were undertaken to evaluate the inflammatory cellular response and the immunoexpression of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in the injured human spinal cord. The cellular sources of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha were elucidated by immunofluorescence double-labeled confocal imaging. RESULTS: : Increased immunoreactivity of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha was detected in neurons 0.5 hour after injury, and in neurons and microglia 5 hours after injury, but the expression of these proinflammatory cytokines was short-lived and declined sharply to baseline by 2 days after injury. In the inflammatory cellular response, as early as 0.5 hour after spinal cord injury, activated microglia were detected, and axonal swellings and axons were surrounded by microglial processes. Numerous neutrophils appeared in the injured cord 1 day after injury, and then their number declined dramatically, whereas macrophages progressively increased after day 1. CONCLUSIONS: Endogenous cells (neurons and microglia) in the human spinal cord, not the blood-borne leukocytes, contribute to the early production of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in the post-traumatic inflammatory response, and microglia are involved the early response to traumatic axonal injury.

Downregulation of amyloid precursor protein (APP) expression following post-traumatic cyclosporin-A administration.

The aim of these studies was to assess and quantitate the effects of cyclosporin-A (CyA) on brain APP messenger RNA and neuronal perikaryal APP antigen expression following controlled focal head impact in sheep. Impact results in a significant increase in both APP mRNA and neuronal perikaryal APP antigen expression. Post-traumatic administration of CyA (intrathecal 10 mg/kg) resulted in a reduction in APP mRNA and neuronal perikaryal antigen expression. At 2 h postinjury, CyA treatment caused a statistically significant (p < 0.05) 1.3 +/- 0.1-fold decrease in APP mRNA in the central gray matter of impacted sheep compared to untreated impacted sheep. A more profound reduction in APP mRNA synthesis (1.6 +/- 0.2 fold) was evident at 6 h (p < 0.05). The mean percentage brain area with APP immunoreactive neuronal perikarya at 6 h post-injury was 94.5% in untreated impacted animals, 10.0% in CyA-treated impacted animals, 5.5% in untreated nonimpacted animals, and 6% in CyA-treated non-impacted controls. These results demonstrate that CyA has a downregulatory effect on increased APP expression caused by TBI.

Impact mechanics and axonal injury in a sheep model.

This paper describes a biomechanical study of axonal injury due to a blunt impact to the head. The aim of the experimental model was to produce axonal injury analogous to that seen in human trauma while measuring the dynamics of the impact and the subsequent kinematics of the head. These measurements were made in a way to facilitate the simulation of these experiments using the finite element method. Sheep were anaesthetised and ventilated, and subjected to a single impact to the lateral aspect of their skull. The impact force was measured throughout the duration of the impact and the kinematics of the head was measured using a novel implementation of a nine-accelerometer array. The axonal injury was identified using amyloid precursor protein (APP) as a marker, intensified using antigen retrieval techniques. Axonal injury was consistently produced in all animals. Commonly injured regions included the sub-cortical and deep white matter, and the periventricular white matter surrounding the lateral ventricles. The observed axonal injury was mapped and quantified on three coronal sections of each brain. The measure used to describe the injury severity correlated with the peak magnitude of the impact force and with peak values of kinematic parameters, particularly the peak change of linear and angular velocity.

Altered subarachnoid space compliance and fluid flow in an animal model of posttraumatic syringomyelia.

STUDY DESIGN: A histologic study of cerebrospinal fluid tracers in Sprague-Dawley rats undergoing lumboperitoneal shunt insertion in the excitotoxic animal model of posttraumatic syringomyelia (PTS). OBJECTIVES: To determine the effects of cerebrospinal fluid (CSF) diversion from the subarachnoid space on perivascular flow (PVS) and syrinx formation in posttraumatic syringomyelia. SUMMARY OF BACKGROUND DATA: In an animal model of PTS, fluid enters syringes from the subarachnoid space via perivascular spaces. Preferential PVS flow occurs at the level of the syrinx. It has been suggested that arachnoiditis predisposes to posttraumatic syringomyelia formation by obstructing subarachnoid cerebrospinal fluid flow and enhancing perivascular flow. MATERIALS AND METHODS: Thirty-two male Sprague-Dawley rats were investigated using the CSF tracer horseradish peroxidase (HRP), the excitotoxic model of PTS, and lumboperitoneal shunt insertion. Five experimental groups consisted of normal controls, syrinx only and shunt only controls, and shunt insertion before or after syrinx formation. In all groups except normal controls, CSF flow studies were performed 6 weeks after the final intervention. Grading scales were used to quantify HRP staining. RESULTS: All excitotoxic model animals formed syringes. Perivascular flow was greatest at the level of the syrinx. Cerebral cortex perivascular flow was significantly reduced after shunt insertion in animals with a syrinx (P < 0.05). Shunt insertion did not alter syrinx length or size. There were no significant differences between shunt and syrinx first groups. CONCLUSIONS: Increasing caudal subarachnoid space compliance with a shunt does not affect local CSF flow into the spinal cord and syrinx. These results suggest that localized alterations in compliance, as opposed to obstruction from traumatic arachnoiditis, may act as an important factor in syrinx pathogenesis.

The role of excitotoxic injury in post-traumatic syringomyelia.

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.

Fluid flow in an animal model of post-traumatic syringomyelia.

More than a quarter of patients with spinal cord injury develop syringomyelia, often with progressive neurological deficit. Treatment options remain limited and long-term failure rates are high. The current poor understanding is impeding development of improved therapies. The source and route of fluid flow into syringes has been investigated using cerebrospinal fluid (CSF) tracers. Previous work using a model of canalicular syringomyelia has shown that fluid enters the dilated central canal from perivascular spaces. The aim of this study was to determine the source and route of fluid flow in an animal model of extracanalicular (post-traumatic) syringomyelia. A model of post-traumatic syringomyelia was established in 25 Sprague-Dawley rats with intraparenchymal injections of quisqualic acid and kaolin-induced arachnoiditis. Rats survived for 6 weeks before injection of the CSF tracer horseradish peroxidase into the cisterna magna. Examination of the spatial distribution of horseradish peroxidase at 0, 3, 5, 10, or 20 min after injection was used to determine the route of fluid flow. Horseradish peroxidase rapidly spread to the ventromedian fissure, perivascular spaces, central canal, and extracanalicular syrinx. Flow occurred into the syrinx prior to significant perivascular flow in the rostral spinal cord. Preferential flow into the syrinx occurred from the perivascular spaces of the central penetrating branches of the anterior spinal artery in the grey matter. Transparenchymal flow into the syrinx was less prominent than perivascular flow. This is the first report of fluid flow within the spinal cord in a model of post-traumatic syringomyelia. Fluid from perivascular spaces moves preferentially into extracanalicular syringes and the surrounding parenchyma. Obstruction to CSF flow and loss of compliance from traumatic arachnoiditis might potentiate fluid flow in the perivascular space.

Ventriculoperitoneal shunt failure as a secondary complication of ovarian hyperstimulation syndrome. Case report.

The authors report on a patient who presented with shunt failure due to ovarian hyperstimulation syndrome (OHSS) following in vitro fertilization treatment. Shunt dysfunction was attributed to intraabdominal hypertension as a consequence of ascites. At surgery, the shunt was found to be patent. The peritoneal catheter was externalized and subsequently revised to become a ventriculoatrial shunt system. This led to clinical improvement in the patient and restoration of ventricular size. Such a shunt complication has not previously been reported. Neurosurgeons should be alerted to this possibility in view of the increasing use of assisted conception in many developed countries.

Camel racing: a new cause of extradural haemorrhage in Australia.

Camel racing is a relatively new sport in Australia. A 52 year old woman fell from her camel during a country race. Although she was wearing an approved equestrian helmet, she suffered a skull fracture and a life-threatening extradural haematoma. Her treatment highlights the key issues of management of head injuries in remote places. A paramount requirement is close collaboration between country medical practitioner, neurosurgeon and retrieval specialist.