A small animal model for early cerebral aneurysm pathology.

Prior studies, using systemic hypertension and elastase infusion, have induced cerebral aneurysm (CA) formation in mice. However, the CAs induced were rapidly formed, relatively large, and often ruptured. These features are not completely representative of human CAs. We set out to develop a mouse model representative of the early pathological features of human CA. Twenty male C57/BL6 mice were placed in a stereotactic frame. Low dose elastase solution (2µl/min) was manually injected into the right basal cistern. Human angiotensin II (0.11µl/h) was infused subcutaneously. Mice were observed for 2-3weeks prior to euthanasia. Early CA histopathological features including endothelial change (EC) and internal elastic lamina degeneration (IELD) were systematically sought at major cerebral arterial bifurcations. Brains were harvested from 11 of 15 mice, yielding 27 bifurcations. Sub-arachnoid haemorrhage (SAH) without CA formation was observed in one brain. Macroscopic CA without SAH was observed in another brain. Early CA features were observed in 8/11 (73%) brains. All bifurcations with IELD demonstrated EC: where EC was absent, IELD was also absent. EC severity appeared to correlate with IELD severity. EC and IELD were both severe within the CA. Using lower dose elastase solution than previously employed, we developed a model of early CA pathology. Our model demonstrated that the spectrum of known early CA pathology can be created at multiple bifurcations in mice, with EC severity appearing to correlate with IELD severity. This model permits the study of factors which potentially advance or retard the progression of CA formation.

Post-traumatic amnesia.

Of patients hospitalised for traumatic brain injury (TBI), most pass through a state of altered consciousness known as "post-traumatic amnesia" (PTA). Despite the lack of a consistent definition, PTA is widely used as a construct in neurosurgical practice to guide decision-making and prognosis. Accurate PTA assessment is important, because over-evaluation leads to excess social, financial and opportunity costs, whilst under-evaluation risks patient welfare. Whilst anterograde memory is certainly disrupted in PTA, PTA in fact involves a far more extensive memory disturbance. More instructively, the complete "post-TBI syndrome" also comprises an extensive cognitive deficit which includes a confusional state, as well as a behavioural disturbance characterised by acute agitation. Recently, impairments in attention and executive functioning have also been emphasised; indeed, some consider these the primary disturbance with PTA. Although all of these features were fully described (or implied) by the earliest pioneers, most current PTA scores do not assess the complete "post-TBI syndrome". Currently, the Westmead PTA scale (WPTAS) directs most in-hospital TBI management throughout Australasia: however, in addition to general defects, specific limitations have been identified in the levels of evidence for WPTAS validity. We review the literature regarding PTA and, in particular, the continued role of the WPTAS in directing neurosurgical practice.

A technique for producing demyelination of the rat optic nerves.

Demyelination is a major cause of neurological disability within the human population, and the end product of a number of pathological processes, though the most common is the disease multiple sclerosis. This disease commonly affects the optic pathway, particularly the optic nerve and chiasm. This paper reports a novel technique of producing chemical glial toxin induced demyelination in the rat optic nerves and chiasm by the direct instillation of the glial toxin ethidium bromide into the rat cranial subarachnoid space causing demyelination of the optic nerves and chiasm. This model, because of its involvement of the optic pathways, will allow both histological and functional assessments of the processes of demyelination and remyelination in the rat animal model.