THE PROBLEM OF ASSESSING EFFECTIVE NEUROPROTECTION IN EXPERIMENTAL CEREBRAL-ISCHEMIA

In animal models of global and focal ischemia neuroprotection is typic ally determined by quantifying the degree of cell loss or reduction in infarct volume shortly after the ischemic insult. These methods are u nable to reliably detect more subtle forms of neuronal death and dysfu nction that arise from injury to non-homogenous cell populations (e.g. hilar and striatal neurons), or to dendrites (e.g. loss of structural proteins or decreased synaptic transmission). It is argued that this type of covert injury contributes to a wide range of functional impair ments (e.g. decreased working memory, altered field potentials, loss o f forelimb dexterity) that are rarely used as outcome measures in expe rimental studies even though they are of paramount importance clinical ly. The limitations of a purely histological approach in assessing neu roprotection are clearly illustrated using examples of protective drug therapies, mild hypothermia and ischemic preconditioning. An alternat ive strategy that incorporates behavioural, electrophysiological and h istological endpoints is put forth as a more powerful method for gaugi ng neuroprotection. The strength of this approach will be increased if these assessments are performed on the same animals. By incorporating functional measures and longer postischemic survival into their exper imental protocols, investigators will increase the validity of their m odels and hopefully reduce the likelihood of advancing ineffective the rapies into costly clinical trials. (C) 1998 Elsevier Science Ltd.