Despite a wealth of recent literature and research on traumatic brain injury, very little has been applicable to diagnosing and treating this syndrome at a tissue level. Part of this problem is the inability to assess rapidly and early in the syndrome the degree or progression of brain injury at a tissue level using simple biochemical analytes. With this in mind, we designed a study in 66 human subjects, who presented with acute blunt head trauma, to determine whether free, ionized serum magnesium (IMg2+) and/or free, ionized serum calcium (ICa2+) levels correlated with the severity of head trauma (HT) and whether any predictive reliable patterns emerge. By using a new ion-selective electrode (ISE) for IMg2+, we have been able to determine IMg2+ and ICa2+ within minutes after sampling in the serum of patients early (1-8 h) after HT. These studies reveal that acute HT is associated with graded deficits (up to 62%, mean = 25%) in serum IMg2+, but not in total serum Mg, which are related to severity of injury based on CT scans and other diagnostic parameters. The greater the degree of injury, the greater the ICa2+/IMg2+ ratio. These ionic findings are compatible with the idea that early ischaemia after head trauma may be important in determining neurological outcome. Our findings provide the first evidence for divalent cation changes in blood after traumatic brain injury, which could be of both diagnostic and prognostic value in patients with traumatic brain injury.

Mitochondrial dysfunction is involved in many neurodegenerative disorders in humans. Here we report mutations in a gene (designated levy) that codes for subunit VIa of cytochrome c oxidase (COX). The mutations were identified by the phenotype of temperature-induced paralysis and showed the additional phenotypes of decreased COX activity, age-dependent bang-induced paralysis, progressive neurodegeneration, and reduced life span. Germ-line transformation using the levy 1 gene rescued the mutant flies from all phenotypes including neurodegeneration. The data from levy mutants reveal a COX-mediated pathway in Drosophila, disruption of which leads to mitochondrial encephalomyopathic effects including neurodegeneration, motor dysfunction, and premature death. The data present the first case of a mutation in a nuclear-encoded structural subunit of COX that causes mitochondrial encephalomyopathy rather than lethality, whereas several previous attempts to identify such mutations have not been successful. The levy mutants provide a genetic model to understand the mechanisms underlying COXmediated mitochondrial encephalomyopathies and to explore possible therapeutic interventions.