Calcium antagonism in neonatal rats with kaolin-induced hydrocephalus.
Juvenile rats with kaolin-induced hydrocephalus have reduced brain injury if treated with nimodipine or magnesium sulfate. Experiments were conducted to determine if the neuroprotective effects could be replicated in neonatal rats with experimental hydrocephalus at an age comparable to prematurely born humans. In a blinded and randomized manner, drugs were administered for 14 days beginning 7 days after induction of hydrocephalus. Nimodipine was given twice daily by subcutaneous injections. Daily doses greater than 38 mg/kg of body weight were fatal. Daily doses of 3.8 to 30 mg/kg were not associated with behavioral, structural, or biochemical improvements. Magnesium chloride was administered via daily subcutaneous minipump infusion (0.87 or 1.74 mM/kg) along with twice daily injections of 0.74 or 1.48 mM/kg. Magnesium sulfate was administered by twice daily subcutaneous doses of 1.54 or 7.72 mM/kg. Sedation occurred, but there was no statistically significant protection in regard to behavior, brain structure, or brain composition in any of the magnesium experiments. Developmental alterations in calcium channels of the neonatal rat brain could account for differences from prior experiments in young hydrocephalic rats.
Khan
Osaama H
OH
Department of Pathology, University of Manitoba, 727 McDermot Avenue, Winnipeg, Manitoba, Canada.
McPhee
Lisa C
LC
Moddemann
Lisa N
LN
Del Bigio
Marc R
MR
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001925:Brain Damage, Chronic / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006849:Hydrocephalus / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D007260:Infusion Pumps; D007616:Kaolin / Q000009:adverse effects; D020547:Lateral Ventricles / Q000473:pathology; D015636:Magnesium Chloride / Q000494:pharmacology / Q000627:therapeutic use; D017616:Magnesium Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D008278:Magnesium Sulfate / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009553:Nimodipine / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D015996:Survival Rate; D016896:Treatment Outcome
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D017616:Magnesium Compounds; D018696:Neuroprotective Agents; D015636:Magnesium Chloride; D007616:Kaolin; D009553:Nimodipine; D008278:Magnesium Sulfate