Glutamate receptors: the cause or cure in perinatal white matter injury?
Glutamate toxicity from hypoxia-ischaemia during the perinatal period causes white matter injury that can result in long-term motor and intellectual disability. Blocking ionotropic glutamate receptors (GluRs) has been shown to inhibit oligodendrocyte injury in vitro, but GluR antagonists have not yet proven helpful in clinical studies. The opposite approach of activating GluRs on developing oligodendrocytes shows promise in experimental studies on rodents as reported by Jartzie et al., in this issue. Group I metabotropic glutamate receptors (mGluRs) are expressed transiently on developing oligodendrocytes in humans during the perinatal period, and the blood-brain-barrier permeable agonist of group I mGluRs, 1-aminocyclopentane-trans-1,3-dicarboxylic acid (ACPD), reduces white matter damage significantly in a rat model of perinatal hypoxia-ischaemia. The results suggest drugs activating this class of GluRs could provide a new therapeutic approach for preventing cerebral palsy and other neurological consequences of diffuse white matter injury in premature infants.
Nervous System Development and Plasticity Section, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. fieldsd@mail.nih.gov
R Douglas
RD
Fields
D000818:Animals; D018683:Excitatory Amino Acid Agents / Q000627:therapeutic use / Q000633:toxicity; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D007223:Infant; D007231:Infant, Newborn; D007969:Leukomalacia, Periventricular / Q000188:drug therapy / Q000209:etiology; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D017470:Receptors, Glutamate / Q000378:metabolism*
D018683:Excitatory Amino Acid Agents; D017470:Receptors, Glutamate