Catalase Activity and Thiobarbituric Acid Reactive Substances (TBARS) Production in a Rat Model of Diffuse Axonal Injury. Effect of Gadolinium and Amiloride Alejandro Santos, 1,2,4 Nuno Borges, 2 Anto´nio Cerejo, 3 Anto´nio Sarmento, 1 and Isabel Azevedo 1 (Accepted April 21, 2005) This study evaluated the effect of mechanogated membrane ion channel blockers on brain catalase (CAT) activity and thiobarbituric acid reactive substances (TBARS) production after traumatic brain injury (TBI). A weight drop trauma model was used. Controls were sham- operated and received no weight drop. Gadolinium (GAD) or amiloride (AMI) were administered to control and experimental rats (30 min after TBI). Brain CAT activity and TBARS production were measured. When blood vessels were washed out with saline perfusion brain CAT activity significantly increased up to 6 h after trauma, decreasing significantly by 24 h; GAD or AMI administration preserved CAT activity 24 h after TBI. TBARS production increased after trauma, this effect being significantly reversed by GAD or AMI administration. GAD significantly decreased TBARS production in control animals. Mechanogated membrane ion channels may be involved in the genesis of the ionic disruption leading to oxidative stress and other secondary injury processes in head trauma. KEY WORDS: Head trauma; rat; catalase; TBARS; mechanogated membrane ion channel blockers. INTRODUCTION Traumatic injuries are the leading cause of mortality in individuals aged 1–44 years, and brain injury signifi- cantly contributes to the outcome in nearly one-half of all deaths from trauma. Most survivors of severe injury are permanently disabled to a lesser or greater degree (1,2). In the United States, Australia, France and Spain the incidence of death from head injury is reported as 20– 30 per 100,000, whereas in the United Kingdom the rate is approximately two thirds lower at 7 per 100,000 (3,4). This major health problem has no current effective pharmacological interventions, most effort being focused on supportive measures (5). Traumatic injury to the central nervous system is regarded as the initial step in a series of biochemical and physiopathological events that may have as a consequence irreversible tissue damage. Several fac- tors are involved in this secondary injury process including ion changes, excitatory amino acids release, formation of reactive oxygen species and metabolic energy perturbations (6,7). Data obtained with animal models of trau- matic brain injury (TBI) show that high levels of 1 Servic¸ o de Bioquı´mica (U38-FCT) Faculdade de Medicina, Universidade do Porto, 4200-319, Porto, Portugal. 2 Faculdade de Cieˆncias da Nutric¸a˜o e Alimentac¸a˜o da Univer- sidade do Porto, 4200-465, Porto, Portugal. 3 Servic¸o de Neurocirurgia, Hospital de S. Joa˜o, Alameda Prof. Hernaˆni Monteiro, 4200, Porto. 4 Address reprint requests to: Alejandro Santos, Servic¸ o de Bioquı´mica (U38-FCT) Faculdade de Medicina. Universidade do Porto. 4200-319 Porto, Portugal. Tel: 351-22-5508838; Fax: 351-22-5508838; E-mail: alejandr@med.up.pt Neurochemical Research, Vol. 30, No. 5, May 2005 (Ó 2005), pp. 625–631 DOI: 10.1007/s11064-005-2750-9 625 0364-3190/05/0500–0625/0 Ó 2005 Springer Science+Business Media, Inc.