THE NEUROPROTECTIVE EFFECTS OF MK-801 ON THE INDUCTION OF MICROGYRIA BY FREEZING-INJURY TO THE NEWBORN RAT NEOCORTEX

Four-layered microgyria is associated with many developmental disorder s, including mental retardation, epilepsy, and developmental dyslexia. Freezing lesions to the newborn rodent neocortex result in the format ion of four-layered microgyria. Previous research had suggested this t ype of injury acts as an hypoxic/ischemic event to the developing cort ical plate. The current study examines the effectiveness of the non-co mpetitive N-methyl-D-aspartate receptor antagonist dizocilpine (MK-801 ) in protecting against freezing injury to the newborn rat cortical pl ate. Three groups of rats received freezing injury to the cortical pla te on the first day of life (postnatal day 1). Two groups were treated with MK-801 (1 or 2 mg/kg) 0.5 h before the lesion and 6 and 14 h aft er, while one group received saline injections. A fourth group receive d MK-801 injections, but did not have a freezing lesion. The volume of neocortical abnormality was determined for all three groups in rats k illed after postnatal day 7. Treatment with the higher dose of MK-801 (3 x 2 mg/kg) dramatically reduced the effects of freezing injury but also resulted in over 50% mortality in both lesioned and unlesioned gr oups. Animals in the lesioned group, however, had a decreased volume o f abnormal cortex, and there were fewer animals with microsulci than i n the untreated group. This is the first demonstration of a significan t anatomical neuroprotective effect in newborns leading to a reduction of cortical malformation.