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Calcium antagonism in neonatal rats with kaolin-induced hydrocephalus
Osaama H Khan1, Lisa C McPhee, Lisa N Moddemann
1Department of Pathology, University of Manitoba, 727 McDermot Avenue, Winnipeg, Manitoba, Canada.
Insights
Nimodipine and magnesium sulfate did not protect neonatal rats with hydrocephalus. Unlike in juvenile rats, these treatments showed no behavioral, structural, or biochemical improvements in neonates.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Hydrocephalus is a condition characterized by excess cerebrospinal fluid in the brain.
- Previous studies suggested nimodipine and magnesium sulfate may offer neuroprotection in juvenile rats with hydrocephalus.
- Neonatal hydrocephalus shares similarities with conditions in prematurely born human infants.
Purpose of the Study:
- To investigate the neuroprotective potential of nimodipine and magnesium sulfate in neonatal rats with experimental hydrocephalus.
- To determine if findings in juvenile rats could be replicated in a neonatal model relevant to premature human infants.
Main Methods:
- Neonatal rats with kaolin-induced hydrocephalus received nimodipine or magnesium sulfate for 14 days, starting 7 days post-induction.
- Drugs were administered via subcutaneous injections or minipump infusions in a blinded, randomized manner.
- Dose-ranging studies were conducted for both nimodipine and magnesium compounds.
Main Results:
- High doses of nimodipine were fatal; lower doses showed no significant behavioral, structural, or biochemical improvements.
- Magnesium sulfate and magnesium chloride treatments did not provide statistically significant neuroprotection.
- Sedation was observed in magnesium-treated groups, but no other adverse effects were noted.
Conclusions:
- Nimodipine and magnesium sulfate lack neuroprotective effects in neonatal rats with hydrocephalus.
- Developmental differences in neonatal rat brain calcium channels may explain the lack of efficacy compared to juvenile models.
- These findings suggest current therapeutic strategies may not be suitable for neonatal hydrocephalus.
Abstract:
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.
