Assessment of experimental neurotrauma

Abstract

Model systems of closed head injury are designed to replicate aspects of traumatic brain injury, ischemia and epilepsy in man. The aim of this thesis was to (1) develop sensitive systems enabling analyses of the biochemical reactions, as reflected by leakage of marker compounds to the cerebrospinal fluid (CSF); and (2) develop and assess a new model for closed head injury and associated dynamic changes in the brain cell. A new approach was developed enabling multiple sampling of cisternal CSF in rats. The approach caused less trauma than previously utilized techniques. The approach was used to evaluate diffuse brain injury, as induced by a short single exposure of rats to intense impulse noise. A transient increase in CSF concentrations of two brain specific cytosolic proteins, neuron specific enolase (NSE) and the glial S-100 protein, occurred during the first two hours. A more prominent response was achieved by the exposure to impulse noise, if the brain was injured the day before.A new model was developed for the induction of closed head injury in rabbits by rotational acceleration. Subarachnoid haemorrhages, focal brain tissue bleedings, diffuse axonal injury, reactive astrocytosis and a raised levels of extracellular excitatory amino acids were observed, corresponding to findings in patients with head injury. Rotational acceleration of the head induced also neuronal apoptosis and expression of immediate early gene products in several brain regions. Excitotoxic and ischemic mechanisms appeared to be involved. It is concluded that the approaches developed for assessment of brain injury enablea better characterisation of the type and extent of damage as compared to techniques available until now.