Introducing NMDA antagonists into clinical practice: why head injury trials?

1. Head injury is the major cause of death and severe disability in young adults. Evidence from clinical studies shows ischaemic brain damage to be the major determinant of bad outcome, and that a proportion of this (perhaps up to 40%) is delayed, thus offering an opportunity for 'prophylactic' therapy. 2. Laboratory studies in several relevant animal models of human head injury (fluid percussion, subdural haematoma, and focal ischaemia by middle cerebral occlusion) indicate that excitatory amino acids are important mediators of brain damage. Pretreatment with NMDA antagonists has shown that the extent of ischaemic damage may be dramatically reduced in these models (68% reduction in the cat MCA occlusion model, 54% in the rat subdural haematoma model). 3. Trials of NMDA antagonists in human head injury are therefore strongly indicated.