Recent biochemical advances in white matter ischaemia.
Stroke is one of the leading causes of death and disability in the developed world and as a result is the focus of intensive research. Historically, investigators in the field have focused on the effects of energy deprivation on the neuronal population, but, in recent times, as imaging techniques have become more advanced, a greater appreciation of the extent of non-neuronal injury has emerged. Initial investigations into the pathophysiology of white matter ischaemia reported damage to central myelinated axons via reversal of the Na+-Ca2+ exchange protein due to Na+ loading and ischaemia-induced membrane depolarisation. The latter also gates voltage-sensitive Ca2+ channels that contribute to the Ca2+ overload both directly and indirectly via Ca2+ release from intracellular stores. Excitotoxicity, once thought the unfortunate preserve of neurons, also contributes to white matter damage via both N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors. However, important physiological differences are apparent in these receptors when compared to those present at the synapse, leading researchers to ask whether the molecular diversity of glutamate receptors will provide successful therapeutic interventions in the future. This brief review aims to summarise recent progress in the field of white matter ischaemia.
Alix
James J P
JJ
University of Leicester Medical School, Leicester, UK. jjpa1@le.ac.uk
D000818:Animals; D001921:Brain / Q000503:physiopathology*; D002545:Brain Ischemia / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use
D018696:Neuroprotective Agents