Drug development for stroke: importance of protecting cerebral white matter

Multiple pharmacological mechanisms have been identified over the last deca de which can protect grey matter from ischaemic damage in experimental mode ls. A large number of drugs targeted at neurotransmitter receptors and rela ted mechanisms involved in ischaemic damage have advanced to clinical trial s in stroke and head injury based on their proven ability to reduce grey ma tter damage in animal models. The outcome to date of the clinical trials of neuroprotective drugs has been disappointing. Although the failure to tran slate preclinical pharmacological insight into therapy is multifactorial, w e propose that the failure to ameliorate ischaemic damage to white matter h as been a major factor. The recent development of quantitative techniques t o assess ischaemic damage to cellular elements in white matter, both axons and oligodendrocytes, allows rigorous evaluation of pharmacologic mechanism s which may protect white matter in ischaemia. Such pharmacological approac hes provide therapeutic opportunities which are both additional or alternat ives to those currently being evaluated in man. (C) 1999 Elsevier Science B .V. All rights reserved.