We examined whether
NPS 1506, a novel uncompetitive
N-methyl-D-aspartate receptor antagonist, influences neurological outcome following
closed head trauma (CHT) in rats. One hundred ten rats were divided into 11 groups: CHT (yes/no), treatment with
NPS 1506 (yes/no), and time of euthanization (24 h/48 h). The dose of
NPS 1506 was 1 mg/kg IV at 1 and 4 hours following CHT or
sham operation.
Closed head trauma induced the following changes in the injured hemisphere: Decreased specific gravity (sg) (1.036 +/- 0.006) and
magnesium (Mg) (0.042 +/- 0.005 microg/mg) at 24 hours, and
potassium (K) at 24 (1.145 +/- 0.376 microg/mg) and 48 hours, and increased water content (W) (84.9 +/- 2.5%) and
sodium (Na) (2.135 +/- 0.699 microg/mg) at 24 hours, and
calcium (Ca) at 24 (0.543 +/- 0.157 microg/mg) and 48 hours. These were reversed by
NPS 1506; sg of 1.043 +/- 0.004, Mg of 0.077 +/- 0.009 microg/mg, K of 1.930 +/- 0.238 microg/mg, W of 81.5 +/- 1.9%, Ca of 0.043 +/- 0.023 microg/mg, and Na of 0.688 +/- 0.110 microg/mg. In groups not given
NPS 1506, a nonsignificant decrease in neurological severity score (NSS) occurred at 24 and 48 hours as compared to NSS at 1 hour after CHT. In groups given
NPS 1506, NSS at 24 and 48 hours decreased significantly (improved) compared to NSS at 1 hour, but not compared to NSS at 24 and 48 hours in groups not given
NPS 1506.
NPS 1506 caused no significant change in ischemic tissue volume or hemorrhagic
necrosis volume in the injured hemisphere at 24 hours or 48 hours. These findings indicate that
NPS 1506 improved measures of brain tissue
edema (at 24 hours but not at 48 hours) and ion homeostasis, and this improvement was not related to other measures of outcome.