Injury-induced alterations in N-methyl-D-aspartate receptor subunit composition contribute to prolonged 45calcium accumulation following lateral fluid percussion.

摘要: Abstract Cells that survive traumatic brain injury are exposed to changes in their neurochemical environment. One of these is a prolonged (48 h) uptake calcium which, by itself, not lethal. The N -methyl- d -aspartate receptor (NMDAR) responsible for the acute membrane flux following trauma; however, it unclear if involved lasting 2 days. We proposed induced molecular change NMDAR modifying concentrations its corresponding subunits (NR1 and NR2). Changing could result being more sensitive glutamate prolong opening, thereby exposing cells sustained calcium. To test this hypothesis, adult rats were subjected lateral fluid percussion NR1, NR2A NR2B measured within different regions. Although little was seen both NR2 decreased nearly 50% compared with controls, particularly ipsilateral cerebral cortex. This decrease 4 days levels retuning control values weeks. However, same subunits, resulting (over 30%) NR2A:NR2B ratio indicating had temporarily become would remain open longer once activated. Combining regional temporal findings 45 autoradiographic studies revealed degree subunit corresponded extent accumulation. Finally, utilizing combination NR2B-specific antagonists determined as much at 85% long term NMDAR-mediated occurs through receptors whose favor subunit. These data indicate TBI induces NMDAR, contributing cells' post-injury vulnerability glutamatergic stimulation.