title: The problem of assessing effective neuroprotection in experimental cerebral ischemia.
abstract: In animal models of global and focal ischemia neuroprotection is typically determined by quantifying the degree of cell loss or reduction in infarct volume shortly after the ischemic insult. These methods are unable to reliably detect more subtle forms of neuronal death and dysfunction that arise from injury to non-homogeneous 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 impairments (e.g. decreased working memory, altered field potentials, loss of forelimb dexterity) that are rarely used as outcome measures in experimental studies even though they are of paramount importance clinically. The limitations of a purely histological approach in assessing neuroprotection are clearly illustrated using examples of protective drug therapies, mild hypothermia and ischemic preconditioning. An alternative strategy that incorporates behavioural, electrophysiological and histological endpoints is put forth as a more powerful method for gauging 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 experimental protocols, investigators will increase the validity of their models and hopefully reduce the likelihood of advancing ineffective therapies into costly clinical trials.
authors.affiliation: Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada. corbett@morgan.ucs.mun.ca
authors.forename: D
authors.initials: D
authors.lastname: Corbett
authors.forename: S
authors.initials: S
authors.lastname: Nurse
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy*; D007036:Hypothermia, Induced; D019194:Ischemic Preconditioning; D018696:Neuroprotective Agents / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents