Excitatory amino acid (EAA)
neurotransmitters may play a role in the pathophysiology of traumatic injury to the CNS. Although
NMDA receptor antagonists have been reported to have therapeutic efficacy in animal models of
brain injury, these compounds may have unacceptable toxicity for clinical use. One alternative approach is to inhibit the release of EAAs following traumatic injury. The present study examined the effects of administration of a novel
sodium channel blocker and EAA release inhibitor, BW1003C87, or the
NMDA receptor-associated
ion channel blocker
magnesium chloride on
cerebral edema formation following experimental
brain injury in the rat. Animals (n = 33) were subjected to fluid percussion
brain injury of moderate severity (2.3 atm) over the left parietal cortex. Fifteen minutes after injury, the animals received a constant infusion of BW1003C87 (10 mg/kg, i.v.),
magnesium chloride (300 mumol/kg, i.v.), or saline over 15 min (2.75 ml/kg/15 min). In all animals, regional tissue water content in brain was assessed at 48 h after injury, using the wet weight/dry weight technique. In saline-treated control animals, fluid percussion
brain injury produced significant regional
brain edema in injured left parietal cortex (p < 0.001), the cortical area adjacent to the site of maximal injury (p < 0.001), left hippocampus (p < 0.001), and left thalamus (p = 0.02) at 48 h after
brain injury. Administration of BW1003C87 15 min postinjury significantly reduced focal
brain edema in the cortical area adjacent to the site of maximal injury (p < 0.02) and left hippocampus (p < 0.01), whereas
magnesium chloride attenuated
edema in left hippocampus (p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)