In
brain injury, concentrations of extracellular
excitatory amino acids are increased and stimulate
glutamate receptors in general and the
N-methyl-D-aspartate (
NMDA)-preferring subtype in particular. That stimulation causes substantial
calcium influx, which appears to initiate a cascade of events leading to neuronal death. Blockage of
NMDA receptors with specific antagonists or noncompetitive
ion channel blockers provides protection against
excitatory amino acid-induced neurotoxicity. We previously reported that the
NMDA receptor antagonist
dizocilpine maleate improved the neurological severity score (NSS) after
head trauma in rats. The present study was designed to determine whether
ketamine, a
NMDA receptor antagonist like
dizocilpine maleate, improves neurological outcome following
head trauma in rats. Thirty-two male Sprague-Dawley rats (235-250 g) were divided into four groups. Groups A and B were surgically prepared only. Groups C and D were surgically prepared and then a nonpenetrating impact was delivered to the cranium over the left hemisphere. Groups A and C received no treatment. Groups B and D were treated with
ketamine, 180 mg/kg i.p., 1 h after
head trauma. The NSS was determined at 1, 2, 4, 10, 24, and 48 h following
head trauma. After killing at 48 h, cortical slices were taken adjacent to the lesion on the traumatized hemisphere and from comparable sites on the nontraumatized hemisphere to measure the tissue specific gravity and water content. Brains were then placed in 4%
formaldehyde and the volume of hemorrhagic
necrosis measured 4 days later.
Head trauma increased the NSS and, in the traumatized hemisphere, decreased the specific gravity, increased the water content, and caused
cerebral infarction. With
ketamine, the NSS at 24 and 48 h following
head trauma was 7.4 +/- 2.6 and 6.7 +/- 2.6 (mean +/- SEM), respectively, significantly improved compared to the NSS in the untreated group of 12.6 +/- 2.6 and 11.3 +/- 2.6, respectively (p <0.02, Mann-Whitney U test). With
ketamine, the volume of hemorrhagic
necrosis was 88.0 +/- 23.1 mm, significantly less than that in the untreated group (147.4 +/- 22.4 mm; p <0.05, unpaired t test). The brain tissue specific gravity and water content at 48 h and the rectal temperature at 4 and 48 h after
head trauma were not significantly different between treated and untreated groups. It is concluded that in this model of closed cranial impact,
ketamine improves neurological outcome and decreases the volume of hemorrhagic
necrosis without altering
brain edema.