A comparison of the protective effect of dexamethasone to other potential prophylactic agents in a neonatal rat model of cerebral hypoxia-ischemia.
It has recently been reported that pretreatment with a single dose of dexamethasone (0.1 mg/kg) 24 hours before hypoxia in 7-day-old rat pups is protective against an hypoxic-ischemic insult (unilateral carotid artery occlusion followed by 3 hours of hypoxia in 8% O2). The authors now examine whether pretreatment 6 hours before insult is equally effective and compare other agents potentially suitable for prophylaxis in neonatal hypoxia-ischemia, including the calcium antagonists flunarizine (30 mg/kg pretreatment), nimodipine (0.5 mg/kg pretreatment), and the 21-aminosteroid U-74389F (10 mg/kg pre- and posttreatment). For each active agent, there was also a vehicle-treated control group. Comparison of the mean area of ipsilateral infarction on brain coronal sections showed that there was no statistically significant difference between the various control groups (mean area of infarction 66% +/- 4%). Pretreatment with dexamethasone 6 hours prior to hypoxia offered complete protection with no infarction. A beneficial effect was seen following pretreatment with flunarizine (mean area of infarction 33.6% +/- 7.8%), although this degree of damage was still significantly different from that seen with dexamethasone pretreatment. Pretreatment with nimodipine or U-74389F offered no protection (mean area of infarction 77.5% +/- 4% and 59% +/- 10%, respectively). Unlike findings in adult animals and clinical studies, the current studies show that dexamethasone may have a role in the treatment of neonatal hypoxia-ischemia and deserves reappraisal.
Chumas
P D
PD
Division of Neurosurgery, Hospital for Sick Children, University of Toronto, Ontario, Canada.
Del Bigio
M R
MR
Drake
J M
JM
Tuor
U I
UI
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D000860:Hypoxia / Q000473:pathology*; D011281:Pregnatrienes / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002121:Calcium Channel Blockers; D011281:Pregnatrienes; C074965:U 74389F; D003907:Dexamethasone