Secondary brain damage, following severe head injury is considered to be a
major cause for Dad outcome. Impressive reductions of the extent of brain d
amage in experimental studies have raised high expectations for cerebral ne
uroprotective treatment, in the clinic. Therefore multiple compounds were a
nd are being evaluated in trials. In this review we discuss the pathomechan
isms of traumatic brain damage, based upon their clinical importance. The r
ole of hypothermia, mannitol, barbiturates, steroids, free radical scavenge
rs, arachidonic acid inhibitors, calcium channel blockers, N-methyl-D-aspar
tate (NMDA) antagonists, and potassium channel blockers, will be discussed.
The importance of a uniform strategic approach for evaluation of potential
ly interesting new compounds in clinical trials, to ameliorate outcome in p
atients with severe head injury, is proposed. To achieve this goal, two non
profit organizations were founded: the European Brain injury Consortium (EB
IC) and the American Brain Injury Consortium (ABIC). Their aim lies in cond
ucting better clinical trials, which incorporate lessons learned from previ
ous trials, such that the succession of negative, or incomplete studies, as
performed in previous years, will cease.