The sodium channel blocker and glutamate release inhibitor BW1003C87 and magnesium attenuate regional cerebral edema following experimental brain injury in the rat.
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)
Okiyama
K
K
Department of Surgery, University of Pennsylvania, Philadelphia 19104-6316.
Smith
D H
DH
Gennarelli
T A
TA
Simon
R P
RP
Leach
M
M
McIntosh
T K
TK
D000818:Animals; D001929:Brain Edema / Q000517:prevention & control*; D001930:Brain Injuries / Q000150:complications*; D018691:Excitatory Amino Acid Antagonists; D015636:Magnesium Chloride / Q000494:pharmacology*; D008297:Male; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers
D018691:Excitatory Amino Acid Antagonists; D011743:Pyrimidines; D026941:Sodium Channel Blockers; D015636:Magnesium Chloride; C078265:5-(2,3,5-trichlorophenyl)pyrimidine-2,4-diamine ethane sulfonate