Relationship of altered glutamate receptor subunit mRNA expression to acute cell loss after spinal cord contusion

Alterations in the expression of ionotropic glutamate receptors (GluR) cont ribute to neuronal loss after brain ischemia and epilepsy. In order to dete rmine whether altered expression of GluR subunits might contribute to cell loss after spinal cord injury (SCI), we performed a time course study of su bunit mRNA expression using quantitative in situ hybridization. Expression was studied in ventral horn motor neurons (VMN) and glia in adjacent ventra l white matter at 15 min and 4, 8, and 24 h after SCI in tissue sections 4 mm rostral and caudal to the injury epicenter. We found that the AMPA subun it GluR2 was significantly downregulated in VMN at 24 h, but not at the ear lier times examined, although half the loss of VMN in these locations occur s by 8 h after injury. No changes in the normal expression of GluR2 or GluR 4 were found in white matter where glial loss occurs after SCI. NMDA subuni ts NR1 and NR2A were significantly and rapidly up-regulated in VMN after SC I, but only caudal to the lesion site, while VMN loss is similar rostral an d caudal to the epicenter. Thus, the temporal pattern of AMPA and the spati al pattern of NMDA subunit expression changes were distinct from the patter n of VMN loss after SCI. We conclude that altered GluR subunit expression a fter SCI is unlikely to be involved in secondary cell loss and instead may be involved with plasticity and reorganization of the injured spinal cord. (C) 2001 Academic Press.